# Pair analysis: exoc3l2a / exoc3l2b  (run 2026-09-28)

## 0. Ensembl Compara homologies of the two zebrafish genes

### exoc3l2a (ENSDARG00000008414)
- within_species_paralog danio_rerio ENSDARG00000030782 exoc3l2b chr15:20139031 level=Osteoglossocephalai
- within_species_paralog danio_rerio ENSDARG00000061714 si:dkey-45k15.1 chr13:7368994 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000043416 tnfaip2a chr20:18661624 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000058180 exoc3l4 chr13:7387822 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000058160 tnfaip2b chr13:7442023 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000014582 exoc3 chr2:50104811 level=Bilateria
- within_species_paralog danio_rerio ENSDARG00000051899 exoc3l1 chr25:14425834 level=Bilateria
- ortholog_one2many lepisosteus_oculatus ENSLOCG00000014731 exoc3l2b chrLG2:66970786 level=Neopterygii
- ortholog_one2many homo_sapiens ENSG00000283632 EXOC3L2 chr19:45210600 level=Euteleostomi
- ortholog_one2many mus_musculus ENSMUSG00000011263 Exoc3l2 chr7:19196973 level=Euteleostomi
- ortholog_one2one oryzias_latipes ENSORLG00000025181 exoc3l2a chr14:2112180 level=Clupeocephala
### exoc3l2b (ENSDARG00000030782)
- within_species_paralog danio_rerio ENSDARG00000008414 exoc3l2a chr5:36752943 level=Osteoglossocephalai
- within_species_paralog danio_rerio ENSDARG00000061714 si:dkey-45k15.1 chr13:7368994 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000043416 tnfaip2a chr20:18661624 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000058180 exoc3l4 chr13:7387822 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000058160 tnfaip2b chr13:7442023 level=Gnathostomata
- within_species_paralog danio_rerio ENSDARG00000014582 exoc3 chr2:50104811 level=Bilateria
- within_species_paralog danio_rerio ENSDARG00000051899 exoc3l1 chr25:14425834 level=Bilateria
- ortholog_one2many lepisosteus_oculatus ENSLOCG00000014731 exoc3l2b chrLG2:66970786 level=Neopterygii
- ortholog_one2many homo_sapiens ENSG00000283632 EXOC3L2 chr19:45210600 level=Euteleostomi
- ortholog_one2many mus_musculus ENSMUSG00000011263 Exoc3l2 chr7:19196973 level=Euteleostomi
- ortholog_one2one oryzias_latipes ENSORLG00000021922 exoc3l2b chr13:484139 level=Clupeocephala

## 1. Human EXOC3-family proteins (UniProt) and their PANTHER subfamilies

- EXOC3 O60645 745 aa; PANTHER PTHR21292:SF13, PTHR21292
- EXOC3L2 Q2M3D2 802 aa; PANTHER PTHR21292:SF7, PTHR21292
- TNFAIP2 Q03169 654 aa; PANTHER PTHR21292, PTHR21292:SF4
- EXOC3L1 Q86VI1 746 aa; PANTHER PTHR21292:SF12, PTHR21292
- EXOC3L4 Q17RC7 722 aa; PANTHER PTHR21292:SF14, PTHR21292

## 1b. Pairwise identities

length exoc3l2a: 932 aa
length exoc3l2b: 917 aa
length EXOC3: 745 aa
length EXOC3L2: 802 aa
length TNFAIP2: 654 aa
length EXOC3L1: 746 aa
length EXOC3L4: 722 aa
length gar_ENSLOCG00000014731: 861 aa
length medaka_ENSORLG00000025181: 919 aa
length medaka_ENSORLG00000021922: 876 aa
length zf_si:dkey-45k15.1: 632 aa
length zf_tnfaip2a: 701 aa
length zf_exoc3l4: 787 aa
length zf_tnfaip2b: 613 aa
length zf_exoc3: 748 aa
length zf_exoc3l1: 780 aa

identity exoc3l2a vs exoc3l2b: 50.9% over 992 columns

| protein | exoc3l2a | exoc3l2b |
|---|---|---|
| EXOC3 | 19.7% (975) | 20.6% (960) |
| EXOC3L2 | 35.3% (970) | 35.9% (955) |
| TNFAIP2 | 20.9% (940) | 21.2% (933) |
| EXOC3L1 | 20.7% (978) | 21.5% (948) |
| EXOC3L4 | 21.8% (987) | 21.9% (983) |
| gar_ENSLOCG00000014731 | 47.5% (953) | 56.2% (931) |
| medaka_ENSORLG00000025181 | 60.2% (959) | 53.3% (981) |
| medaka_ENSORLG00000021922 | 48.6% (956) | 64.3% (945) |
| zf_si:dkey-45k15.1 | 16.7% (970) | 18.3% (954) |
| zf_tnfaip2a | 18.2% (972) | 20.5% (955) |
| zf_exoc3l4 | 22.2% (990) | 21.5% (973) |
| zf_tnfaip2b | 17.3% (961) | 18.1% (936) |
| zf_exoc3 | 20.9% (967) | 21.2% (951) |
| zf_exoc3l1 | 20.8% (1007) | 20.8% (979) |

Outgroup proteins vs human family members (identity %):
| outgroup | EXOC3 | EXOC3L2 | TNFAIP2 | EXOC3L1 | EXOC3L4 |
|---|---|---|---|---|---|
| gar_ENSLOCG00000014731 | 22.2 | 38.5 | 22.3 | 21.4 | 23.6 |
| medaka_ENSORLG00000025181 | 19.4 | 34.9 | 20.7 | 20.5 | 20.6 |
| medaka_ENSORLG00000021922 | 21.9 | 36.6 | 23.0 | 22.8 | 22.4 |
| zf_si:dkey-45k15.1 | 18.4 | 18.6 | 20.4 | 17.4 | 19.9 |
| zf_tnfaip2a | 21.7 | 20.0 | 25.7 | 19.4 | 21.8 |
| zf_exoc3l4 | 21.0 | 23.2 | 21.5 | 21.6 | 23.0 |
| zf_tnfaip2b | 19.0 | 17.8 | 28.4 | 19.1 | 19.0 |
| zf_exoc3 | 74.3 | 22.2 | 21.2 | 28.0 | 23.2 |
| zf_exoc3l1 | 32.3 | 24.2 | 23.0 | 36.8 | 22.8 |

## 2. Identity inside/outside the Pfam Sec6 domain of human EXOC3L2; patient-variant sites

Pfam PF06046 on human EXOC3L2 (Q2M3D2): 270-719
N-terminal (before Sec6) [1-269] exoc3l2a: aligned 244/269, identical 117/269 (43.5%)
Sec6 domain [270-719] exoc3l2a: aligned 445/450, identical 194/450 (43.1%)
C-terminal (after Sec6) [720-802] exoc3l2a: aligned 75/83, identical 31/83 (37.3%)
human EXOC3L2 residues G41->A, A72->T in exoc3l2a
N-terminal (before Sec6) [1-269] exoc3l2b: aligned 242/269, identical 116/269 (43.1%)
Sec6 domain [270-719] exoc3l2b: aligned 444/450, identical 200/450 (44.4%)
C-terminal (after Sec6) [720-802] exoc3l2b: aligned 78/83, identical 27/83 (32.5%)
human EXOC3L2 residues G41->N, A72->S in exoc3l2b
N-terminal (before Sec6) [1-269] gar_ENSLOCG00000014731: aligned 253/269, identical 124/269 (46.1%)
Sec6 domain [270-719] gar_ENSLOCG00000014731: aligned 449/450, identical 187/450 (41.6%)
C-terminal (after Sec6) [720-802] gar_ENSLOCG00000014731: aligned 68/83, identical 33/83 (39.8%)
human EXOC3L2 residues G41->N, A72->G in gar_ENSLOCG00000014731

## 3. Tajima-style relative-rate test (outgroup = gar)

gar positions aligned in both copies: 829
changes unique to exoc3l2a (m1): 138; unique to exoc3l2b (m2): 71; chi2 (1 df) = 21.48 (P<0.05)

## 4. Whole-embryo time course, E-ERAD-475 (TPM, median of replicates)

| stage | exoc3l2a | exoc3l2b |
|---|---|---|
| zygote | 0 | 0 |
| cleavage 2-cell | 0 | 0 |
| blastula 128-cell | 0 | 0.3 |
| blastula 1k-cell | 0 | 0.5 |
| blastula dome | 0 | 0 |
| gastrula 50%-epiboly | 0 | 0 |
| gastrula shield | 0 | 0 |
| gastrula 75%-epiboly | 0 | 0 |
| segmentation 1-4 somites | 0.4 | 0 |
| segmentation 14-19 somites | 2 | 0 |
| segmentation 20-25 somites | 0.9 | 1 |
| pharyngula prim-5 | 2 | 3 |
| pharyngula prim-15 | 4 | 3 |
| pharyngula prim-25 | 7 | 1 |
| hatching long-pec | 4 | 2 |
| larval protruding mouth | 7 | 8 |
| larval day 4 | 10 | 13 |
| larval day 5 | 9 | 10 |

## 5. Bgee expressed calls per anatomical entity (expression score 0-100; only 'expressed' calls are returned)

### exoc3l2a: 16 calls
- swim bladder: 92.7 (gold; RNA-Seq)
- head kidney: 77.0 (gold; RNA-Seq)
- intestine: 74.5 (gold; RNA-Seq)
- muscle tissue: 61.9 (gold; RNA-Seq)
- bone element: 56.1 (gold; RNA-Seq)
- zone of skin: 54.7 (gold; RNA-Seq)
- heart: 49.7 (silver; RNA-Seq)
- early embryo: 48.9 (gold; RNA-Seq)
- granulocyte: 44.7 (silver; RNA-Seq)
- tail: 41.3 (gold; RNA-Seq)
- larva: 41.1 (gold; RNA-Seq)
- liver: 40.0 (silver; RNA-Seq)
- blastula: 38.2 (silver; RNA-Seq)
- head: 35.5 (silver; EST,RNA-Seq)
- testis: 31.9 (silver; RNA-Seq)
- pharyngeal gill: 31.7 (silver; RNA-Seq)
### exoc3l2b: 17 calls
- intestine: 91.2 (gold; RNA-Seq)
- spleen: 82.4 (gold; RNA-Seq)
- pharyngeal gill: 82.0 (gold; RNA-Seq)
- mesonephros: 71.7 (gold; EST,RNA-Seq)
- head kidney: 67.1 (gold; RNA-Seq)
- bone element: 64.1 (gold; RNA-Seq)
- liver: 61.1 (gold; Affymetrix,RNA-Seq)
- granulocyte: 58.7 (gold; RNA-Seq)
- heart: 57.7 (gold; Affymetrix,RNA-Seq)
- zone of skin: 51.7 (gold; RNA-Seq)
- muscle tissue: 45.1 (gold; RNA-Seq)
- tail: 44.9 (gold; Affymetrix,RNA-Seq)
- blastula: 43.2 (gold; Affymetrix,RNA-Seq)
- larva: 42.5 (gold; Affymetrix,RNA-Seq)
- ovary: 37.3 (silver; RNA-Seq)
- head: 28.3 (silver; Affymetrix,EST,RNA-Seq)
- testis: 26.4 (silver; RNA-Seq)
### gar ENSLOCG00000014731: 14 calls
- intestine: 75.0 (gold; RNA-Seq)
- pharyngeal gill: 70.7 (gold; RNA-Seq)
- mesonephros: 68.9 (gold; RNA-Seq)
- embryo: 67.7 (gold; RNA-Seq)
- testis: 66.9 (gold; RNA-Seq)
- liver: 66.1 (gold; RNA-Seq)
- heart: 58.6 (gold; RNA-Seq)
- zone of skin: 53.7 (gold; RNA-Seq)
- camera-type eye: 44.4 (gold; RNA-Seq)
- larva: 43.8 (gold; RNA-Seq)
- bone element: 40.3 (gold; RNA-Seq)
- ovary: 37.6 (silver; RNA-Seq)
- muscle tissue: 37.0 (silver; RNA-Seq)
- brain: 30.5 (gold; RNA-Seq)

entities with a call for exoc3l2a only: ['early embryo', 'swim bladder']
entities with a call for exoc3l2b only: ['mesonephros', 'ovary', 'spleen']
entities with a call for both: ['blastula', 'bone element', 'granulocyte', 'head', 'head kidney', 'heart', 'intestine', 'larva', 'liver', 'muscle tissue', 'pharyngeal gill', 'tail', 'testis', 'zone of skin']

## 6. ZFIN curated wild-type expression (wildtype-expression_fish.txt)

### exoc3l2a (ZDB-GENE-060526-343): 0 rows
### exoc3l2b (ZDB-GENE-100728-5): 4 rows
- hindbrain (dorsal region); Pharyngula:Prim-5 to Larval:Protruding-mouth; mRNA in situ hybridization; ZDB-PUB-100518-8
- neural crest; Segmentation:5-9 somites to Segmentation:5-9 somites; mRNA in situ hybridization; ZDB-PUB-100518-8
- pharyngeal arch; Pharyngula:Prim-5 to Larval:Protruding-mouth; mRNA in situ hybridization; ZDB-PUB-100518-8
- whole organism; Segmentation:5-9 somites to Segmentation:5-9 somites; Reverse transcription PCR; ZDB-PUB-100518-8

## 7. Synteny (Ensembl REST)

exoc3l2a: chr5:36752943-36763394
exoc3l2b: chr15:20139031-20190052
human EXOC3L2: chr19:45210600
human EXOC3L4: chr14:103094538
human TNFAIP2: chr14:103121265
gar ortholog ENSLOCG00000014731: LG2:66970786

### Neighbours of exoc3l2a (+/- 1.5 Mb): 87 protein-coding genes (1 homology queries failed)
Teleost-level zebrafish paralogues of these neighbours that lie on chr15 (chromosome of exoc3l2b):
- nova1 -> nova2 (chr15:28685625, 8.50 Mb from exoc3l2b; level Osteoglossocephalai)
- panx1b -> panx1a (chr15:2475894, 17.66 Mb from exoc3l2b; level Osteoglossocephalai)
- zgc:153990 -> zgc:113149 (chr15:29140126, 8.95 Mb from exoc3l2b; level Osteoglossocephalai)
- tmprss4b -> tmprss4a (chr15:12429206, 7.71 Mb from exoc3l2b; level Clupeocephala)
- dlb -> dlc (chr15:20463448, 0.27 Mb from exoc3l2b; level Osteoglossocephalai)
- ppp1r14aa -> ppp1r14ab (chr15:20204628, 0.01 Mb from exoc3l2b; level Osteoglossocephalai)
- mark4a -> mark4b (chr15:23550890, 3.36 Mb from exoc3l2b; level Clupeocephala)
- scn4bb -> scn4ba (chr15:12466852, 7.67 Mb from exoc3l2b; level Osteoglossocephalai)
- ckma -> ckmb (chr15:23643718, 3.45 Mb from exoc3l2b; level Clupeocephala)
- apoa1a -> apoa1b (chr15:102925, 20.04 Mb from exoc3l2b; level Osteoglossocephalai)
- hnrnpl -> hnrnpl2 (chr15:5784212, 14.35 Mb from exoc3l2b; level Clupeocephala)
Neighbours whose human orthologue lies within 5 Mb of human EXOC3L2: 3
- kptn -> KPTN (+2.26 Mb)
- mark4a -> MARK4 (-0.13 Mb)
- slc8a2a -> SLC8A2 (+2.22 Mb)
Neighbours whose human orthologue lies within 5 Mb of human EXOC3L4: 0
Neighbours whose human orthologue lies within 5 Mb of human TNFAIP2: 0
Neighbours whose gar orthologue lies within 5 Mb of gar ENSLOCG00000014731: 13
- alkbh6 -> alkbh6 (+0.27 Mb)
- arhgap35b -> arhgap35b (+1.30 Mb)
- capns1a -> capns1b (+0.19 Mb)
- ckma -> ckmb (+0.12 Mb)
- gjd1a -> gjd1a (-4.94 Mb)
- hnrnpl -> hnrnpl2 (-4.23 Mb)
- kptn -> kptn (-4.34 Mb)
- mark4a -> mark4b (+0.08 Mb)
- nccrp1 -> nccrp1 (-3.93 Mb)
- nfkbib -> nfkbib (-4.90 Mb)
- nova1 -> nova1 (+0.54 Mb)
- slc8a2a -> slc8a2a (-4.20 Mb)
- srsf7a -> srsf7a (-4.21 Mb)

### Neighbours of exoc3l2b (+/- 1.5 Mb): 56 protein-coding genes (0 homology queries failed)
Teleost-level zebrafish paralogues of these neighbours that lie on chr5 (chromosome of exoc3l2a):
- tbcela -> tbcelb (chr5:63248266, 26.48 Mb from exoc3l2a; level Clupeocephala)
- usf1 -> usf1l (chr5:29803380, 6.95 Mb from exoc3l2a; level Osteoglossocephalai)
- ppp1r14ab -> ppp1r14aa (chr5:36730726, 0.02 Mb from exoc3l2a; level Osteoglossocephalai)
- ubash3bb -> ubash3ba (chr5:29851433, 6.90 Mb from exoc3l2a; level Osteoglossocephalai)
- bco2b -> bco2a (chr5:30052714, 6.70 Mb from exoc3l2a; level Osteoglossocephalai)
- bco2b -> bco2l (chr5:26121393, 10.63 Mb from exoc3l2a; level Osteoglossocephalai)
- sdhdb -> sdhda (chr5:30081241, 6.67 Mb from exoc3l2a; level Clupeocephala)
- dlc -> dlb (chr5:36693859, 0.06 Mb from exoc3l2a; level Osteoglossocephalai)
Neighbours whose human orthologue lies within 5 Mb of human EXOC3L2: 0
Neighbours whose human orthologue lies within 5 Mb of human EXOC3L4: 0
Neighbours whose human orthologue lies within 5 Mb of human TNFAIP2: 0
Neighbours whose gar orthologue lies within 5 Mb of gar ENSLOCG00000014731: 5
- chp2 -> chp2 (-0.36 Mb)
- plekhg2 -> ENSLOCG00000014720 (-0.11 Mb)
- rnaset2l -> rnaset2l (-0.37 Mb)
- spint2 -> spint2 (-0.05 Mb)
- timm50 -> timm50 (-0.28 Mb)