Ciliary transition zone MKS, NPHP and CEP290 modules

The ciliary transition zone (TZ) is the proximal region of the cilium, just distal to the basal body, where Y-shaped links connect the axonemal microtubules to the ciliary membrane. It acts as a gate that controls which proteins enter and leave the cilium. In nematodes and mammals the TZ is built from the same set of conserved, ciliopathy-associated protein modules. An RPGRIP1L-family assembly hub (MKS-5 in C. elegans) is needed for essentially all other TZ proteins to reach the TZ. CEP290 is a large coiled-coil protein that binds microtubules and membranes; in C. elegans it is a core component of the central cylinder and is needed to localise the MKS module but not the NPHP module. The MKS module contains the three B9-domain proteins MKS1, B9D1 and B9D2, the C2-domain protein CC2D2A, the Tectonic proteins and several transmembrane proteins (TMEM67/meckelin, TMEM216, TMEM107, TMEM231, TMEM237, TMEM17, TMEM218). The NPHP module contains the nephrocystins NPHP1 and NPHP4. The MKS and NPHP modules are partially redundant. Loss of one module leaves cilia nearly normal, whereas combined loss of both causes severe defects in nematodes and mice: the basal body and TZ fail to attach to the membrane, Y-links are lost, axonemes are malformed and non-ciliary membrane proteins leak into the cilium. A further CEP290-dependent branch containing TMEM138 and CDKL1 belongs to neither module. Mutations in the human genes cause Meckel-Gruber syndrome, Joubert syndrome and nephronophthisis. In mammals the nephrocystins also act at epithelial cell-cell junctions, a role outside this module.

MODULE:ciliary_transition_zoneDRAFTCONCRETECellular Componentmodules/ciliary_transition_zone.yaml
ciliary transition zoneGO:0035869 ciliary transition zone assemblyGO:1905349
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
Eight C. elegans TZ proteins form two functional modules that together attach the basal body/TZ to the membrane and establish the ciliary gate.
MKS/MKSR/NPHP proteins establish basal body/TZ membrane attachments before or coinciding with intraflagellar transport-dependent axoneme extension and subsequently restrict accumulation of nonciliary components within the ciliary compartment
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
Module assignment is based on synthetic genetic interactions: mutations within one module do not enhance each other, whereas MKS plus NPHP combinations do.
Thus, we group MKS-1, MKSR-1, MKSR-2, MKS-3, and MKS-6 into an MKS/MKSR module and NPHP-1 and NPHP-4 into an NPHP module
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
MKS-5 is the foundation of two assembly pathways, one for the NPHP module and one for the MKS module with CEP-290 at its core.
In this model, MKS-5 (Rpgrip1L/Rpgrip1 orthologue) represents the foundation of two distinct assembly pathways for the MKS and NPHP modules, with the MKS pathway having CEP-290 as its core
PMID:26540106
Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.
The MKS-NPHP synthetic interaction found in worms is conserved in mice.
These genetic interactions in nematodes predicted mammalian genetic interactions, as combining mouse Tctn1 and Nphp4 mutations also resulted in synthetic ciliary phenotypes.
PMID:21565611
Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways.
Mammalian interaction mapping resolves the same proteins into an NPHP1-4-8 module, a separate NPHP5-6 (CEP290) module and an MKS module.
Our data show that NPHP-JBTS-MKS proteins form an interaction network that can be classified into three distinct modules: “NPHP1-4-8”, “NPHP5-6”, and “Mks”.
PMID:25150219
NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone.
In Chlamydomonas, NPHP4 and CEP290 occupy separate TZ domains and are incorporated independently, as in the animal model.
NPHP4 is stably incorporated into the distal part of the flagellar transition zone, close to the membrane and distal to CEP290, another transition zone protein. Therefore, these two proteins, which are incorporated into the transition zone independently of each other, define different domains of the transition zone.
file:modules/intraflagellar_transport.yaml
Intraflagellar transport
IFT trains pass through the TZ; IFT builds the axoneme after the TZ has been assembled and docked, and is modelled separately.
file:modules/bbsome.yaml
BBSome ciliary trafficking complex module
The BBSome, which traffics membrane cargo across the TZ, is modelled separately and treated as an interface.
file:projects/CAEEL_CILIOPATHY.md
C. elegans Ciliopathy/IFT Pathway Project
Project page listing the worm MKS and NPHP transition-zone genes whose gene reviews ground the C. elegans representatives of this module.

Generalisation. This module was first written as a C. elegans-only module (c_elegans_ciliary_transition_zone) and was generalised to Bilateria. Each role is a FAMILY with the C. elegans protein and, where a gene review exists, the human ortholog as representative members. The C. elegans genetics (synthetic defects between but not within modules, and the localisation hierarchy) still provide most of the evidence for the module boundary. The same boundary is supported in mammals by mouse Tctn1;Nphp4 synthetic phenotypes (PMID:26540106), by the NPHP1-4-8, NPHP5-6 and MKS interaction modules (PMID:21565611) and by the Tctn1-containing MKS complex (PMID:21725307). Taxon scope. The context is Bilateria because the module structure, not just the presence of the genes, has been tested only in nematodes and mammals. Many of these proteins are older. In Chlamydomonas NPHP4 sits at the distal TZ near the membrane, distal to CEP290, and the two are incorporated independently (PMID:25150219), which matches the separation of the CEP290 and NPHP roles here. A TMEM17 paper describes TMEM17 as conserved across ciliated eukaryotes (PMID:40841990). Whether the MKS-NPHP redundancy and the RPGRIP1L-family hub hold outside animals has not been tested in the cached evidence, so the broader clade is not asserted. Redundancy. The genetic redundancy between the MKS and NPHP modules is the defining property of this system. It is recorded in the root description, the part descriptions and the evidence rather than as a connection, because the connection vocabulary has no relation for redundancy. The RPGRIP1L-family hub is the exception to module assignment: mks-5 interacts genetically with members of both modules. The human RPGRIP1L review places RPGRIP1L (NPHP8) in the NPHP complex, because it binds NPHP4 directly (PMID:21565611); it is modelled here as the hub part, consistent with the worm assembly data. CEP290. CEP290 is modelled as its own part, distinct from the MKS module, following the human CEP290 review and the mammalian NPHP5-6 module. In C. elegans it behaves genetically like an MKS-module assembly factor and is needed to localise MKS-module proteins and TMEM-138/CDKL-1. Whether worm CEP-290 needs MKS-5 to reach the TZ is disputed: Li et al. 2016 (PMID:26982032) report that it does, while Schouteden et al. 2015 (PMID:26124290) found CCEP-290 recruitment unaffected in mks-5 mutants. The hub-to-CEP290 connection is therefore recorded with that caveat. The worm gene symbol is ccep-290 (WormBase); the literature also writes CEP-290. MKS module layering. Worm TMEM-107 occupies an intermediate layer of the MKS module and recruits MKS-1, TMEM-231, JBTS-14/TMEM237 and TMEM-17 (PMID:26595381). TMEM-17 and TMEM-218 are peripheral members whose loss does not disrupt the core. TCTN-1 is assigned to the MKS module on genetic grounds (synthetic defects with nphp-1 and nphp-4 but not with MKS-module genes); unlike mouse Tctn1 it is not needed to localise the other worm TZ proteins tested (PMID:26540106). TMEM138 branch. Worm TMEM-138 and CDKL-1 need MKS-5 and CEP-290 for TZ localisation but behave as neither MKS nor NPHP module proteins (PMID:26982032). TMEM-138 is modelled as an optional part, not as an MKS-module member. CDKL-1 has no gene review and is named in text only. Not modelled. NPHP-2/inversin (genes/worm/nphp-2) localises to the inversin compartment distal to the TZ and is outside this boundary. The mammalian NPHP1/NPHP4 roles at epithelial cell-cell junctions are recorded in their gene reviews and are outside this boundary. Human TMEM216, TMEM107, TMEM231, TMEM237, TMEM17 and TMEM218 have no gene reviews yet, so those roles carry only the C. elegans representative. Gene names. MKSR-2 and MKSR-1 were earlier named TZA-1 (B9D2) and TZA-2 (B9D1), and MKS-1 was XBX-7 (PMID:18337471). JBTS-14 is also called TMEM-237. Molecular functions. MFs follow the gene reviews' core functions. Most TZ reviews assert no GO MF, because none fits a structural TZ subunit and the generic structural molecule activity term is not used here; those annotons carry a preferred_term only. Where the worm and human reviews differ, the annoton description says which review asserts the MF. PANTHER grounding. Family ids are given only where the worm and human representatives share the PANTHER family or subfamily in their UniProt records, or where the worm protein's family is named for the protein (TMEM107, TMEM237, TMEM138). The ids were checked against interpro/panther/panther.obo. CEP290 is left without a family id because the worm and human proteins fall in different PANTHER families (PTHR43941 and PTHR18879). MKS-2/TMEM216 and TMEM-17 share PTHR13531, whose name does not describe either protein, and TMEM-231 is in PTHR14605, so those are also left without ids. Interfaces. IFT (MODULE:intraflagellar_transport) and the BBSome (MODULE:bbsome) act after or alongside the TZ: IFT rates are largely normal in worm TZ mutants, and IFT and BBS proteins are not needed to form the TZ or to dock it to the membrane (PMID:21422230). NPHP-1 and NPHP-4 do modulate ciliary access of IFT components (PMID:18316409).

6Nodes
5Parts
0Variant Sets
0Variants
17Annotons
5Connections

Derived QC

Recommended-field compliance

78.3% recommended fields populated
  • knowledge_gaps[0].provenance[0] · reference_section_type (0/1)
  • knowledge_gaps[0].provenance[1] · reference_section_type (0/1)
  • knowledge_gaps[1].provenance[0] · reference_section_type (0/1)
  • knowledge_gaps[2].provenance[0] · reference_section_type (0/1)
  • knowledge_gaps[2].provenance[1] · reference_section_type (0/1)

Module deep research

✗ none found

No MODULE:ciliary_transition_zone deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • mks5_assembly_hub → cep290_module [NOT_CHECKED]
    Localisation hierarchy in TZ assembly, not a reaction chain.
  • cep290_module → mks_module [NOT_CHECKED]
    Localisation hierarchy in TZ assembly, not a reaction chain.
  • mks5_assembly_hub → mks_module [NOT_CHECKED]
    Localisation hierarchy in TZ assembly, not a reaction chain.
  • mks5_assembly_hub → nphp_module [NOT_CHECKED]
    Localisation hierarchy in TZ assembly, not a reaction chain.
  • cep290_module → tmem138_branch [NOT_CHECKED]
    Localisation hierarchy in TZ assembly, not a reaction chain.

Function consistency and core coverage

4 gene-function check(s) reflected in core functions · 0 conflict(s) · 40 evidence or coverage gap(s) (44 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
mks5_scaffold MKS-5 (C. elegans)
UniProtKB:Q09459
Family Representative 		molecular adaptor activity
GO:0060090 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mks5_scaffold RPGRIP1L (human)
UniProtKB:Q68CZ1
Family Representative 		molecular adaptor activity
GO:0060090 		Function Unreviewed
No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
cep290_scaffold CCEP-290 (C. elegans)
UniProtKB:A2A266
Family Representative 		microtubule binding
GO:0008017 		Function Unreviewed
No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
cep290_scaffold CEP290 (human)
UniProtKB:O15078
Family Representative 		microtubule binding
GO:0008017 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mks1_b9 MKS-1 (C. elegans)
UniProtKB:A0A679L8Q5
Family Representative 		B9-domain TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks1_b9 MKS1 (human)
UniProtKB:Q9NXB0
Family Representative 		B9-domain TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mksr1_b9 MKSR-1 (C. elegans)
UniProtKB:Q21191
Family Representative 		B9-domain TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mksr1_b9 B9D1 (human)
UniProtKB:Q9UPM9
Family Representative 		B9-domain TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mksr2_b9 MKSR-2 (C. elegans)
UniProtKB:Q9N423
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Function Unreviewed
No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
mksr2_b9 B9D2 (human)
UniProtKB:Q9BPU9
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mks2_tmem216 MKS-2 (C. elegans)
UniProtKB:C8JQP7
Family Representative 		transmembrane TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks3_tmem67 MKS-3 (C. elegans)
UniProtKB:Q20046
Family Representative 		transmembrane TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks3_tmem67 TMEM67 (human)
UniProtKB:Q5HYA8
Family Representative 		transmembrane TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks6_cc2d2a MKS-6 (C. elegans)
UniProtKB:Q21303
Family Representative 		C2-domain TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks6_cc2d2a CC2D2A (human)
UniProtKB:Q9P2K1
Family Representative 		C2-domain TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tctn_tectonic TCTN-1 (C. elegans)
UniProtKB:O44478
Family Representative 		Tectonic-domain TZ component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tctn_tectonic TCTN1 (human)
UniProtKB:Q2MV58
Family Representative 		Tectonic-domain TZ component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tmem107_intermediate TMEM-107 (C. elegans)
UniProtKB:H2L2K0
Family Representative 		transmembrane TZ component that recruits an MKS submodule
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tmem231_core TMEM-231 (C. elegans)
UniProtKB:Q22804
Family Representative 		transmembrane TZ structural component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tmem237_jbts14 JBTS-14 (C. elegans)
UniProtKB:Q20687
Family Representative 		transmembrane TZ component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tmem17_peripheral TMEM-17 (C. elegans)
UniProtKB:Q23481
Family Representative 		peripheral transmembrane TZ component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tmem218_peripheral TMEM-218 (C. elegans)
UniProtKB:Q2A955
Family Representative 		peripheral transmembrane TZ component
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
nphp4_adaptor NPHP-4 (C. elegans)
UniProtKB:G5ECP0
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nphp4_adaptor NPHP4 (human)
UniProtKB:O75161
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Function Unreviewed
No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
nphp1_scaffold NPHP-1 (C. elegans)
UniProtKB:O17972
Family Representative 		TZ scaffold component of the NPHP module
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
nphp1_scaffold NPHP1 (human)
UniProtKB:O15259
Family Representative 		TZ scaffold component of the NPHP module
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tmem138_component TMEM-138 (C. elegans)
UniProtKB:Q7YX41
Family Representative 		transition-zone membrane protein of unknown activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks5_scaffold RPGRIP1L/MKS-5 family
PANTHER:PTHR14240
Family 		molecular adaptor activity
GO:0060090 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR14240.
cep290_scaffold CEP290 orthologs
Family 		microtubule binding
GO:0008017 		Family Id Missing
The family has no identifier linking it to a curated family review.
mks1_b9 MKS1 subfamily of B9-domain proteins
PANTHER:PTHR12968:SF4
Family 		B9-domain TZ structural component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
mksr1_b9 B9D1 subfamily of B9-domain proteins
PANTHER:PTHR12968:SF1
Family 		B9-domain TZ structural component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
mksr2_b9 B9D2 subfamily of B9-domain proteins
PANTHER:PTHR12968:SF2
Family 		protein-macromolecule adaptor activity
GO:0030674 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12968:SF2.
mks2_tmem216 TMEM216 orthologs
Family 		transmembrane TZ structural component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
mks3_tmem67 meckelin family
PANTHER:PTHR21274
Family 		transmembrane TZ structural component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
mks6_cc2d2a CC2D2A orthologs
PANTHER:PTHR20837
Family 		C2-domain TZ structural component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tctn_tectonic Tectonic family
PANTHER:PTHR14611
Family 		Tectonic-domain TZ component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tmem107_intermediate TMEM107 orthologs
PANTHER:PTHR34341
Family 		transmembrane TZ component that recruits an MKS submodule
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tmem231_core TMEM231 orthologs
Family 		transmembrane TZ structural component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tmem237_jbts14 TMEM237 orthologs
PANTHER:PTHR28388
Family 		transmembrane TZ component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tmem17_peripheral TMEM17 orthologs
Family 		peripheral transmembrane TZ component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tmem218_peripheral TMEM218 orthologs
Family 		peripheral transmembrane TZ component
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
nphp4_adaptor nephrocystin-4 subfamily
PANTHER:PTHR31043:SF3
Family 		protein-macromolecule adaptor activity
GO:0030674 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR31043:SF3.
nphp1_scaffold nephrocystin-1 subfamily
PANTHER:PTHR15176:SF1
Family 		TZ scaffold component of the NPHP module
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
tmem138_component TMEM138 orthologs
PANTHER:PTHR13306
Family 		transition-zone membrane protein of unknown activity
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.

Gene-review completeness (27/27 grounded genes reviewed)

25 complete review(s) · 17 with deep research · 0 missing review · 10 reviewed but lacking deep research

Gene Review Complete Deep research
B9D1 Q9UPM9 ✓ ✓ ✗
B9D2 Q9BPU9 ✓ ✓ ✓
CC2D2A Q9P2K1 ✓ ✓ ✓
ccep-290 A2A266 ✓ ✓ ✗
CEP290 O15078 ✓ 99/101 ✓
jbts-14 Q20687 ✓ ✓ ✗
mks-1 A0A679L8Q5 ✓ ✓ ✓
mks-2 C8JQP7 ✓ ✓ ✗
mks-3 Q20046 ✓ ✓ ✓
mks-5 Q09459 ✓ ✓ ✓
mks-6 Q21303 ✓ ✓ ✓
MKS1 Q9NXB0 ✓ ✓ ✓
mksr-1 Q21191 ✓ ✓ ✓
mksr-2 Q9N423 ✓ ✓ ✓
nphp-1 O17972 ✓ 16/17 ✓
nphp-4 G5ECP0 ✓ ✓ ✓
NPHP1 O15259 ✓ ✓ ✓
NPHP4 O75161 ✓ ✓ ✓
RPGRIP1L Q68CZ1 ✓ ✓ ✓
tctn-1 O44478 ✓ ✓ ✗
TCTN1 Q2MV58 ✓ ✓ ✓
tmem-107 H2L2K0 ✓ ✓ ✗
tmem-138 Q7YX41 ✓ ✓ ✗
tmem-17 Q23481 ✓ ✓ ✗
tmem-218 Q2A955 ✓ ✓ ✗
tmem-231 Q22804 ✓ ✓ ✗
TMEM67 Q5HYA8 ✓ ✓ ✓

Details

Context
BilateriaNCBITaxon:33213
ciliated cells, e.g. nematode amphid and phasmid sensory neurons and mammalian ciliated epithelia
Ciliary transition zone MKS, NPHP and CEP290 modulesCellular Componentciliary_transition_zone

The RPGRIP1L-family assembly hub, CEP290 and the partially redundant MKS and NPHP modules that build the transition zone, dock it to the membrane and establish the ciliary gate.

ciliary transition zoneGO:0035869 ciliary transition zone assemblyGO:1905349
Context
BilateriaNCBITaxon:33213
ciliated cells, e.g. nematode amphid and phasmid sensory neurons and mammalian ciliated epithelia
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
Within-module mutant combinations lack additive defects, while any B9 gene mutation combined with nphp-1 or nphp-4 causes severe cilia anomalies.
For example, even triple B9 gene (mks-1, mksr-1, and mksr-2) or nphp-1;nphp-4 double mutants lack prominent (additive) ciliary defects
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
Combining B9 and nephrocystin mutations causes severe cilia defects.
In contrast, disrupting any B9 gene together with nphp-1 or nphp-4 results in severe cilia anomalies
PMID:18337471
Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis.
The B9 proteins act redundantly with the nephrocystins in ciliogenesis.
Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons.
PMID:26540106
Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.
Tctn1 interacts synthetically with Nphp1 and Nphp4 in both nematodes and mice.
These results reveal that in both nematodes and mice, Tctn1 displays a synthetic genetic interaction with both Nphp1 and Nphp4.

Connections

Li et al. 2016 report that worm CEP-290 needs the MKS-5 coiled-coil region to reach the TZ; Schouteden et al. 2015 found CCEP-290 recruitment unaffected in mks-5 mutants. The dependency is disputed.
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
Worm CEP-290 is lost from the TZ in mks-5 mutants.
In contrast, CEP-290 localisation to the TZ is lost when the core assembly factor, MKS-5, is ablated (Fig 4B).
PMID:26124290
The ciliary transition zone functions in cell adhesion but is dispensable for axoneme assembly in C. elegans.
CCEP-290 recruitment to the TZ is unaffected in mks-5 mutants.
CCEP-290 recruitment was unaffected in mutants of MKS-5, MKSR-2, and NPHP-4, the most upstream components of the MKS and NPHP assembly pathways
In worms CEP-290 is required for MKS-module proteins to reach the TZ.
MKS-5 is required for every MKS-module protein to reach the TZ.
MKS-5 is needed for normal NPHP-1 and NPHP-4 distribution at the TZ; the dependency is partial.
TMEM-138 and CDKL-1 need CEP-290 (and MKS-5) to localise to the TZ.
Part 1: TZ assembly hub required for both modules
RPGRIP1L/MKS-5 transition-zone assembly hubProtein Complexmks5_assembly_hub

The RPGRIP1L-family protein (MKS-5 in worms) localises to the TZ through its coiled-coil region, which is necessary and sufficient for TZ targeting in C. elegans. In mks-5 mutants every known MKS-module protein fails to reach the TZ and NPHP-1 and NPHP-4 are partly mislocalised. mks-5 mutations interact genetically with mutations in both modules. In mammals RPGRIP1L (NPHP8) binds NPHP4 directly.

Annotons

RPGRIP1L/MKS-5 TZ scaffold
mks5_scaffold
Participant: Family: RPGRIP1L/MKS-5 family
Family:
RPGRIP1L/MKS-5 familyPANTHER:PTHR14240 The PANTHER family also contains RPGRIP1, the vertebrate paralog; MKS-5 is the single worm member.
Representative Members: MKS-5 (C. elegans)UniProtKB:Q09459 RPGRIP1L (human)UniProtKB:Q68CZ1

Function

molecular adaptor activityGO:0060090 Scaffold that recruits and anchors MKS-module proteins and, in part, the NPHP module at the TZ. The MF is asserted by the mks-5 review; the human RPGRIP1L review asserts no MF.

Processes

protein localization to ciliary transition zoneGO:1904491 ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869

Foundation of TZ assembly; links the MKS and NPHP modules.

PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
mks-5 mutants fail to localise the whole MKS module and partially alter NPHP-module distribution.
mks-5 mutants fail to localize MKS-1, MKSR-1, MKSR-2, MKS-3, and MKS-6 (i.e., the entire known MKS/MKSR module) to the TZ; the mks-5 mutation also partially alters NPHP-1 and NPHP-4 distribution at the TZ
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
MKS-5 is the exception to module assignment and links the two modules.
Based on our data, we propose that the MKS/MKSR and NPHP modules are functionally linked through MKS-5
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
The MKS-5 coiled-coil region targets it to the TZ.
Notably, the coiled coil region is both necessary and sufficient for MKS-5 localisation to the TZ
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
MKS-5 is needed to assemble all known worm TZ proteins.
MKS-5 (mammalian Rprgrip1L/Rpgrip1 orthologue) is essential for the assembly of all known TZ proteins (including CEP-290)
PMID:21565611
Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways.
Mammalian NPHP4 binds RPGRIP1L (NPHP8) directly.
We find that NPHP4 directly binds both NPHP1 and NPHP8 in vitro
Part 2: CEP290 central TZ scaffold and MKS-branch assembly factor
CEP290 central TZ moduleProtein Complexcep290_module

CEP290 is a large coiled-coil protein that binds microtubules through a central region and membranes through its N-terminal domain. In C. elegans CCEP-290 is a core component of the central cylinder, the inner scaffold of the TZ, and is needed for TZ localisation of MKS-module proteins and of TMEM-138 and CDKL-1, but not of MKS-5 or the NPHP module. In mammals CEP290 (NPHP6) forms a separate NPHP5-6 interaction module rather than belonging to the MKS module.

Annotons

CEP290 microtubule- and membrane-binding TZ scaffold
cep290_scaffold
Participant: Family: CEP290 orthologs
Family:
CEP290 orthologs No PANTHER family id is asserted: UniProt places worm CCEP-290 in PTHR43941 and human CEP290 in PTHR18879.
Representative Members: CCEP-290 (C. elegans)UniProtKB:A2A266 CEP290 (human)UniProtKB:O15078

Function

microtubule bindingGO:0008017 Asserted by the human CEP290 review, which also asserts lipid binding (GO:0008289) by the N-terminal membrane-binding domain; together they are thought to tether the axoneme to the membrane. The worm ccep-290 review asserts no MF.

Processes

ciliary transition zone assemblyGO:1905349 protein localization to ciliary transition zoneGO:1904491

Locations

ciliary transition zoneGO:0035869 central cylinderGO:1990805
PMID:24051377
Disruption of CEP290 microtubule/membrane-binding domains causes retinal degeneration.
CEP290 binds both membranes and microtubules.
we have shown that CEP290 is capable of directly binding to both cellular membranes and microtubules, possibly anchoring the two to each other and likely playing a key structural role in the maintenance of the cilium
PMID:26124290
The ciliary transition zone functions in cell adhesion but is dispensable for axoneme assembly in C. elegans.
Worm CCEP-290 is a core component of the TZ central cylinder.
with CCEP-290 serving as a core component of the central cylinder, which appears to act as an inner scaffold for transition zone assembly
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
Worm CEP-290 is an assembly factor specific for MKS-module components.
we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
CEP-290 is needed for a functional TZ gate.
Together, our two complementary TZ functional assays suggest that CEP-290 plays an essential role in maintaining a functional TZ “gate” or membrane diffusion barrier.
Part 3: MKS module
MKS moduleProtein Complexmks_module

The MKS module comprises the B9-domain trio MKS1, B9D1 and B9D2, whose TZ localisation is interdependent, the C2-domain protein CC2D2A, the Tectonic proteins and the transmembrane proteins TMEM67/meckelin, TMEM216, TMEM107, TMEM231, TMEM237, TMEM17 and TMEM218. Its TZ localisation depends on the RPGRIP1L-family hub and, in worms, on CEP-290. Within the module, worm TMEM-107 forms an intermediate layer that recruits MKS-1, TMEM-231, JBTS-14 and TMEM-17. Mutants lacking one or several MKS-module proteins have nearly normal cilia; combined with NPHP-module mutations they cause severe ciliogenesis defects. In mammals the complex (also called the tectonic or B9 complex) acts as a membrane diffusion barrier.

MKS complexGO:0036038
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
Mutations within the MKS module do not enhance each other.
Other mutant combinations such as mks-1;mks-3, or mks-6;mksr-2, do not noticeably disrupt cilia
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
CEP-290 is needed for MKS-module, but not NPHP-module, TZ localisation.
CEP-290 is required for the localisation of MKS module components but is not essential for the largely normal TZ localisation of the NPHP module or MKS-5
PMID:32726168
Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is essential as a diffusion barrier for ciliary membrane proteins.
In human cells the B9 complex is needed for the TZ membrane diffusion barrier.
On the basis of these observations, we conclude that formation of the heterotrimeric B9D complex is essential for the TZ to function as a diffusion barrier for membrane proteins.

Annotons

MKS1 B9-domain protein
mks1_b9
Participant: Family: MKS1 subfamily of B9-domain proteins
Family:
MKS1 subfamily of B9-domain proteinsPANTHER:PTHR12968:SF4
Representative Members: MKS-1 (C. elegans)UniProtKB:A0A679L8Q5 MKS1 (human)UniProtKB:Q9NXB0

Function

B9-domain TZ structural component No GO MF is asserted; the human MKS1 review asserts none and the worm mks-1 review lists only protein binding.

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869
PMID:18337471
Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis.
The three worm B9 proteins form a complex at the base of cilia.
the C. elegans B9 proteins form a complex that localizes to the base of cilia
PMID:19208769
Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.
B9-protein TZ localisation is largely co-dependent.
Their subcellular localization is largely co-dependent, pointing to a functional relationship between the proteins.
PMID:32726168
Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is essential as a diffusion barrier for ciliary membrane proteins.
Human MKS1, B9D2 and B9D1 form a linear heterotrimer with interdependent TZ localisation.
We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ
B9D1/MKSR-1 B9-domain protein
mksr1_b9
Participant: Family: B9D1 subfamily of B9-domain proteins
Family:
B9D1 subfamily of B9-domain proteinsPANTHER:PTHR12968:SF1
Representative Members: MKSR-1 (C. elegans)UniProtKB:Q21191 B9D1 (human)UniProtKB:Q9UPM9

Function

B9-domain TZ structural component No GO MF is asserted; the human B9D1 review asserts none.

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869
B9D2/MKSR-2 B9-domain protein
mksr2_b9
Participant: Family: B9D2 subfamily of B9-domain proteins
Family:
B9D2 subfamily of B9-domain proteinsPANTHER:PTHR12968:SF2
Representative Members: MKSR-2 (C. elegans)UniProtKB:Q9N423 B9D2 (human)UniProtKB:Q9BPU9

Function

protein-macromolecule adaptor activityGO:0030674 Asserted by the human B9D2 review: B9D2 bridges MKS1 and B9D1 in the B9 complex. The worm mksr-2 review asserts no specific MF.

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869
PMID:41165761
Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis.
The B9 complex anchors TMEM67 to the TZ membrane.
We also found that the B9 complex interacts with and anchors TMEM67 to the TZ membrane, thereby stabilizing the MKS module and maintaining the integrity of the TZ diffusion barrier.
TMEM216/MKS-2 transmembrane protein
mks2_tmem216
Participant: Family: TMEM216 orthologs
Family:
TMEM216 orthologs Human TMEM216 has no gene review here, so only the worm protein is listed.
Representative Members: MKS-2 (C. elegans)UniProtKB:C8JQP7

Function

transmembrane TZ structural component No GO MF is asserted.

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
MKS-2/TMEM216 is a core MKS-module protein.
The MKS module includes MKS-1 (mammalian Mks1 orthologue), MKSR-1 (B9d1/Mksr1), MKSR-2 (B9d2/Mksr2), MKS-2 (Mks2/Tmem216), MKS-3 (Mks3/Tmem67/Meckelin), MKS-6 (Mks6/Cc2d2a)
TMEM67/MKS-3 meckelin
mks3_tmem67
Participant: Family: meckelin family
Family:
meckelin familyPANTHER:PTHR21274
Representative Members: MKS-3 (C. elegans)UniProtKB:Q20046 TMEM67 (human)UniProtKB:Q5HYA8

Function

transmembrane TZ structural component No GO MF is asserted for the TZ role. The human TMEM67 review asserts Wnt-protein binding and filamin binding for its roles in non-canonical Wnt signalling and basal-body positioning, which are outside this module.

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869
CC2D2A/MKS-6 C2-domain protein
mks6_cc2d2a
Participant: Family: CC2D2A orthologs
Family:
CC2D2A orthologsPANTHER:PTHR20837
Representative Members: MKS-6 (C. elegans)UniProtKB:Q21303 CC2D2A (human)UniProtKB:Q9P2K1

Function

C2-domain TZ structural component No GO MF is asserted; neither gene review asserts one.

Processes

protein localization to ciliary transition zoneGO:1904491

Locations

ciliary transition zoneGO:0035869
Tectonic TCTN-1/TCTN1
tctn_tectonic
Participant: Family: Tectonic family
Family:
Tectonic familyPANTHER:PTHR14611 Worm TCTN-1 is the single ortholog of vertebrate TCTN1-3.
Representative Members: TCTN-1 (C. elegans)UniProtKB:O44478 TCTN1 (human)UniProtKB:Q2MV58

Function

Tectonic-domain TZ component No GO MF is asserted; neither gene review asserts one.

Processes

protein localization to ciliary transition zoneGO:1904491

Locations

ciliary transition zoneGO:0035869
PMID:21725307
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
Mouse Tctn1 forms a complex with MKS-module and other ciliopathy proteins.
Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a.
PMID:21725307
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
Tctn1 is needed to localise Mks1 and Tmem67 to the TZ in mouse cells.
In contrast, Tctn1−/− MEFs exhibited decreased Mks1 and Tmem67 localization to the transition zone
PMID:26540106
Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.
Worm TCTN-1 and NPHP-4 act redundantly for ciliary structure.
Thus, we conclude that ciliary structure is dependent on the overlapping functions of TCTN-1 and NPHP-4.
TMEM107 intermediate-layer MKS recruiter
tmem107_intermediate
Participant: Family: TMEM107 orthologs
Family:
TMEM107 orthologsPANTHER:PTHR34341 Human TMEM107 has no gene review here, so only the worm protein is listed.
Representative Members: TMEM-107 (C. elegans)UniProtKB:H2L2K0

Function

transmembrane TZ component that recruits an MKS submodule No GO MF is asserted; the tmem-107 review asserts none.

Processes

protein localization to ciliary transition zoneGO:1904491

Locations

ciliary transition zoneGO:0035869
PMID:26595381
TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome.
TMEM-107 occupies an intermediate layer of the MKS module and recruits MKS-1, TMEM-231 and JBTS-14.
nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237)
PMID:26595381
TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome.
TMEM-107 acts redundantly with NPHP-4.
functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors
TMEM231 core MKS membrane protein
tmem231_core
Participant: Family: TMEM231 orthologs
Family:
TMEM231 orthologs No PANTHER id is asserted (worm TMEM-231 is classified in PTHR14605, whose name does not describe it). Human TMEM231 has no gene review here.
Representative Members: TMEM-231 (C. elegans)UniProtKB:Q22804

Function

transmembrane TZ structural component No GO MF is asserted; the tmem-231 review asserts none.

Processes

protein localization to ciliary transition zoneGO:1904491

Locations

ciliary transition zoneGO:0035869
PMID:25869670
TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone.
TMEM-231 controls the composition of the TZ and the ciliary membrane.
TMEM-231 is a TZ protein that interacts functionally with other TZ proteins to control the composition of the TZ and ciliary membrane.
TMEM237/JBTS-14 MKS membrane protein
tmem237_jbts14
Participant: Family: TMEM237 orthologs
Family:
TMEM237 orthologsPANTHER:PTHR28388 Human TMEM237 has no gene review here, so only the worm protein is listed.
Representative Members: JBTS-14 (C. elegans)UniProtKB:Q20687

Function

transmembrane TZ component No GO MF is asserted; the jbts-14 review asserts none.

Processes

non-motile cilium assemblyGO:1905515

Locations

ciliary transition zoneGO:0035869
PMID:22152675
TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.
jbts-14 interacts genetically with nphp-4 in TZ membrane anchoring.
Caenorhabditis elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein, to control basal body-TZ anchoring to the membrane and ciliogenesis
TMEM17 peripheral MKS membrane protein
tmem17_peripheral
Participant: Family: TMEM17 orthologs
Family:
TMEM17 orthologs No PANTHER id is asserted (see notes). Human TMEM17 has no gene review here.
Representative Members: TMEM-17 (C. elegans)UniProtKB:Q23481

Function

peripheral transmembrane TZ component No GO MF is asserted; the tmem-17 review asserts none.

Processes

non-motile cilium assemblyGO:1905515

Locations

ciliary transition zoneGO:0035869
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
TMEM-17 is an MKS-module protein that needs CEP-290 for TZ localisation.
elegans TMEM-17 is an MKS module protein [30] that depends on CEP-290 for TZ localisation
PMID:40841990
Missense Variants in the Second Transmembrane Domain of TMEM17 Disrupt Its Stability and Function and Lead to a Wide Phenotypic Spectrum of Ciliopathies.
tmem-17 acts redundantly with nphp-4.
In contrast, double mutant combining nphp‐4 with any tmem‐17 mutants exhibits significant dye‐filling defects, affecting both head and tail cilia.
TMEM218 peripheral MKS membrane protein
tmem218_peripheral
Participant: Family: TMEM218 orthologs
Family:
TMEM218 orthologs The worm protein has no PANTHER classification in UniProt. Human TMEM218 has no gene review here.
Representative Members: TMEM-218 (C. elegans)UniProtKB:Q2A955

Function

peripheral transmembrane TZ component No GO MF is asserted; the tmem-218 review asserts none.

Processes

non-motile cilium assemblyGO:1905515

Locations

ciliary transition zoneGO:0035869
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
TMEM-218 interacts genetically with nphp-4 but not mks-2.
Altogether, our findings that tmem-218 encodes a TZ protein and genetically interacts with nphp-4 but not mks-2 are consistent with TMEM-218 representing a novel MKS module protein.
Part 4: NPHP module
NPHP moduleProtein Complexnphp_module

NPHP1 and NPHP4 localise to the TZ; in Chlamydomonas NPHP4 sits at the distal TZ close to the membrane. In C. elegans nphp-1;nphp-4 double mutants lack additive ciliary defects, but loss of either nephrocystin causes subtle axonemal ultrastructure defects and changes ciliary access of IFT and signalling proteins, and NPHP-4 is needed to localise NPHP-1 in worms and mice. Combined with MKS-module mutations they cause severe ciliogenesis defects. The NPHP module assembles at the ciliary base with MKS-5 even without CEP-290. In mammals NPHP1, NPHP4 and RPGRIP1L (NPHP8) form the NPHP1-4-8 interaction module, which also acts at epithelial cell-cell junctions.

NPHP complexGO:1990957
PMID:18316409
The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure.
NPHP-1 and NPHP-4 act at the TZ to regulate ciliary access of IFT machinery, axonemal components and signalling molecules.
We propose that NPHP-1 and NPHP-4 act globally at the TZ to regulate ciliary access of the IFT machinery, axonemal structural components, and signaling molecules
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
MKS-5 and the NPHP module still localise at the ciliary base in cep-290 mutants.
However, MKS-5::tdTomato and NPHP module proteins (NPHP-1::CFP, NPHP-4::YFP) retain their localisation at the base of cilia (in the same region as the TZ) in the cep-290 mutant.
PMID:26540106
Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.
Nphp4 is needed to localise Nphp1 in mice as in worms.
Hence, mouse Nphp4 is required for the localization of Nphp1, as it is in C.

Annotons

NPHP4 nephrocystin-4
nphp4_adaptor
Participant: Family: nephrocystin-4 subfamily
Family:
nephrocystin-4 subfamilyPANTHER:PTHR31043:SF3
Representative Members: NPHP-4 (C. elegans)UniProtKB:G5ECP0 NPHP4 (human)UniProtKB:O75161

Function

protein-macromolecule adaptor activityGO:0030674 Asserted by the worm nphp-4 review; the human NPHP4 review asserts no MF for the TZ role.

Processes

protein localization to ciliary transition zoneGO:1904491

Locations

ciliary transition zoneGO:0035869
PMID:25150219
NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone.
In Chlamydomonas NPHP4 is part of a TZ barrier for membrane and soluble proteins.
Therefore, NPHP4 functions at the transition zone as an essential part of a barrier that regulates both membrane and soluble protein composition of flagella.
NPHP1 nephrocystin-1
nphp1_scaffold
Participant: Family: nephrocystin-1 subfamily
Family:
nephrocystin-1 subfamilyPANTHER:PTHR15176:SF1
Representative Members: NPHP-1 (C. elegans)UniProtKB:O17972 NPHP1 (human)UniProtKB:O15259

Function

TZ scaffold component of the NPHP module No GO MF is asserted for the TZ role in either gene review. The human NPHP1 review asserts proline-rich region binding for its SH3-domain role at cell-cell junctions, outside this module.

Processes

non-motile cilium assemblyGO:1905515

Locations

ciliary transition zoneGO:0035869
PMID:16885411
Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia.
Mammalian nephrocystin-1 localises to the TZ.
nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
Part 5: CEP290-dependent TMEM138 branch (neither MKS nor NPHP module) (optional)
TMEM138/CDKL-1 CEP290-dependent branchProtein Complextmem138_branch

In C. elegans, TMEM-138 and the kinase CDKL-1 need MKS-5 and CEP-290 to reach the TZ but not core MKS- or NPHP-module proteins, and they show no synthetic ciliogenesis defects with either module. They are proposed to form a separate CEP-290-associated branch. A clear in vivo requirement for worm TMEM-138 in cilium formation has not been shown. Optional because the branch has been characterised only in worms.

Annotons

TMEM138 transition-zone membrane protein
tmem138_component
Participant: Family: TMEM138 orthologs
Family:
TMEM138 orthologsPANTHER:PTHR13306 Human TMEM138 has no gene review here, so only the worm protein is listed.
Representative Members: TMEM-138 (C. elegans)UniProtKB:Q7YX41

Function

transition-zone membrane protein of unknown activity No GO MF is asserted; the tmem-138 review asserts none.

Locations

ciliary transition zoneGO:0035869
PMID:26982032
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
CDKL-1 and TMEM-138 need MKS-5 and CEP-290 for TZ localisation and behave as neither MKS- nor NPHP-module proteins.
Here, we show that two proteins (CDKL-1 and TMEM-138) that require MKS-5 for TZ localisation and do not behave as either MKS or NPHP module proteins depend on CEP-290 for their correct localisation.