# VPS50

> Gene · canonical: https://sugi.bio/atlas/gene/VPS50/
> Atlas v1.13.0 · generated 2026-10-14T18:20:41+00:00

## Summary

**VPS50** (VPS50 subunit of EARP/GARPII complex, HGNC:25956) is a protein-coding gene on chromosome 7q21.2-q21.3, encoding **Syndetin** (Q96JG6). Acts as a component of the EARP complex that is involved in endocytic recycling.

Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex.

*Source: [NCBI Gene 55610](https://www.ncbi.nlm.nih.gov/gene/55610) — automated summary from GO annotations (Alliance of Genome Resources).*

**At a glance**

- **Gene–disease (curated):** neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis (Strong, GenCC)
- **GWAS associations:** 1
- **Clinical variants (ClinVar):** 160 total — 4 pathogenic, 5 likely-pathogenic
- **Expression (HPA):** Low tissue specificity — highest in white matter, corpus callosum, spinal cord
- **GTEx eGene:** eQTL in 27 tissues, sQTL in 18 (q < 0.05)
- **Phenotypes (HPO):** 22
- **Constraint (gnomAD):** pLI 0.11 (intermediate), LOEUF 0.78 (unconstrained)
- **MANE Select transcript:** `NM_017667`




## Identifiers

### Gene identifiers

| Field | Value |
| --- | --- |
| HGNC ID | HGNC:25956 |
| Approved symbol | VPS50 |
| Name | VPS50 subunit of EARP/GARPII complex |
| Location | 7q21.2-q21.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | KIAA1861, FLJ20097, DKFZp313I2429, VPS54L |
| Ensembl gene | ENSG00000004766 |
| Ensembl biotype | protein_coding |
| OMIM | 616465 |
| Entrez | 55610 |

## Gene structure

### Transcript identifiers

**Ensembl transcripts: 39** — 21 protein_coding, 8 retained_intron, 7 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

**MANE Select:** `ENST00000305866`

**Transcript support level (Ensembl TSL; 1 = fully mRNA-supported):** TSL 1: 5, TSL 2: 5, TSL 3: 1, TSL 4: 5, TSL 5: 4

`ENST00000305866`, `ENST00000251739`, `ENST00000436177`, `ENST00000438395`, `ENST00000441602`, `ENST00000443443`, `ENST00000458530`, `ENST00000458707`, `ENST00000467326`, `ENST00000471188`, `ENST00000474412`, `ENST00000476413`, `ENST00000477572`, `ENST00000477935`, `ENST00000480943`, `ENST00000484954`, `ENST00000485140`, `ENST00000485994`, `ENST00000495039`, `ENST00000544910`, `ENST00000649152`, `ENST00000869628`, `ENST00000869629`, `ENST00000869630`, `ENST00000869631`, `ENST00000869632`, `ENST00000869633`, `ENST00000920042`, `ENST00000963423`, `ENST00000963424`, `ENST00000963425`, `ENST00000963426`, `ENST00000963427`, `ENST00001032288`, `ENST00001032289`, `ENST00001032290`, `ENST00001117558`, `ENST00001122932`, `ENST00001142416`

**RefSeq mRNA: 3** — MANE Select: `NM_017667`
`NM_001257998`, `NM_017667`, `NM_024553`

**CCDS:** `CCDS43617`, `CCDS5630`, `CCDS59065`

#### Canonical transcript exons

`ENST00000305866` — 28 exons

| Exon | Start | End |
| --- | --- | --- |
| ENSE00001349954 | 93349875 | 93350033 |
| ENSE00001879893 | 93358317 | 93361123 |
| ENSE00003468743 | 93271220 | 93271262 |
| ENSE00003469430 | 93272635 | 93272733 |
| ENSE00003479133 | 93256509 | 93256562 |
| ENSE00003483098 | 93353640 | 93353761 |
| ENSE00003492725 | 93239866 | 93239934 |
| ENSE00003511769 | 93355891 | 93356080 |
| ENSE00003530590 | 93341427 | 93341575 |
| ENSE00003533024 | 93303460 | 93303550 |
| ENSE00003534212 | 93334117 | 93334197 |
| ENSE00003540140 | 93305828 | 93306004 |
| ENSE00003543253 | 93291703 | 93291835 |
| ENSE00003554361 | 93323611 | 93323732 |
| ENSE00003556503 | 93276165 | 93276305 |
| ENSE00003556643 | 93311166 | 93311272 |
| ENSE00003562954 | 93297145 | 93297243 |
| ENSE00003566532 | 93294545 | 93294636 |
| ENSE00003573662 | 93296742 | 93296836 |
| ENSE00003592176 | 93232366 | 93232500 |
| ENSE00003592963 | 93258159 | 93258276 |
| ENSE00003599572 | 93259550 | 93259632 |
| ENSE00003605983 | 93308824 | 93308942 |
| ENSE00003633039 | 93257394 | 93257464 |
| ENSE00003649318 | 93253860 | 93253931 |
| ENSE00003649326 | 93252653 | 93252775 |
| ENSE00003687917 | 93258357 | 93258392 |
| ENSE00003692642 | 93348711 | 93348807 |

### Expression profiles

**Bgee:** expression breadth **ubiquitous**, 257 present calls, max score 95.97.

**FANTOM5 (CAGE):** breadth **ubiquitous**, TPM avg 23.6909 / max 488.0229, expressed in 1802 samples.

**Highest expression (Bgee):** calcaneal tendon, endothelial cell, tibialis anterior, adrenal tissue, Brodmann (1909) area 46.

#### Genetic regulation across tissues (GTEx eQTL / sQTL)

VPS50 is an **eGene** in GTEx v10 — its expression is genetically regulated (eQTL) in **27** tissues and its splicing (sQTL) in **18** (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant's alternative allele.

showing 20 of 45 significant tissue × QTL associations:

| Tissue | QTL | q-value | Slope | Lead variant |
| --- | --- | --- | --- | --- |
| Nerve Tibial | eqtl | 2.3e-34 | +0.83 | 7:93308804:A:G |
| Skin Sun Exposed Lower leg | eqtl | 2.2e-15 | +0.41 | 7:93308804:A:G |
| Artery Tibial | eqtl | 7.7e-14 | +0.41 | 7:93308804:A:G |
| Artery Tibial | sqtl | 9.3e-14 | -0.80 | 7:93232313:C:T |
| Skin Not Sun Exposed Suprapubic | eqtl | 4.6e-13 | +0.42 | 7:93308804:A:G |
| Thyroid | eqtl | 1.0e-12 | +0.48 | 7:93308804:A:G |
| Testis | eqtl | 5.3e-12 | -0.38 | 7:93178064:C:T |
| Stomach | eqtl | 1.2e-11 | +0.63 | 7:93308804:A:G |
| Skin Sun Exposed Lower leg | sqtl | 2.1e-11 | +0.48 | 7:93340651:G:A |
| Nerve Tibial | sqtl | 9.2e-11 | +0.51 | 7:93340651:G:A |
| Pancreas | eqtl | 9.8e-11 | +0.87 | 7:93309939:G:A |
| Adipose Subcutaneous | eqtl | 1.2e-09 | +0.58 | 7:93236689:TAAG:T |
| Lung | eqtl | 1.4e-09 | +0.27 | 7:93308804:A:G |
| Colon Transverse | eqtl | 2.5e-09 | +0.44 | 7:93308804:A:G |
| Brain Cerebellar Hemisphere | sqtl | 6.5e-09 | -0.43 | 7:93355940:T:C |
| Artery Aorta | eqtl | 2.1e-08 | +0.39 | 7:93308804:A:G |
| Breast Mammary Tissue | sqtl | 8.6e-08 | +0.45 | 7:93340651:G:A |
| Esophagus Muscularis | eqtl | 4.0e-07 | -0.16 | 7:93355940:T:C |
| Adipose Subcutaneous | sqtl | 5.5e-07 | +0.38 | 7:93316698:T:G |
| Colon Sigmoid | eqtl | 1.2e-06 | +0.41 | 7:93309939:G:A |

#### FANTOM5 promoters

2 alternative TSS:

| Promoter ID | TPM avg | Samples expressed |
| --- | --- | --- |
| 79554 | 23.6867 | 1802 |
| 79555 | 0.0042 | 1 |

#### Top tissues by expression

showing 100 of 266 tissues by Bgee expression score (0-100, higher = more expressed):

| Tissue | Anatomy ID | Expression score | Quality |
| --- | --- | --- | --- |
| calcaneal tendon | UBERON:0003701 | 95.97 | gold quality |
| endothelial cell | CL:0000115 | 94.74 | gold quality |
| tibialis anterior | UBERON:0001385 | 94.49 | gold quality |
| adrenal tissue | UBERON:0018303 | 94.47 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 93.35 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 92.11 | gold quality |
| tendon | UBERON:0000043 | 91.92 | gold quality |
| cortical plate | UBERON:0005343 | 91.55 | gold quality |
| Brodmann (1909) area 23 | UBERON:0013554 | 90.97 | gold quality |
| secondary oocyte | CL:0000655 | 90.78 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 90.50 | gold quality |
| postcentral gyrus | UBERON:0002581 | 90.38 | gold quality |
| sperm | CL:0000019 | 90.37 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 90.33 | gold quality |
| ileal mucosa | UBERON:0000331 | 90.29 | gold quality |
| oocyte | CL:0000023 | 90.27 | gold quality |
| colonic epithelium | UBERON:0000397 | 90.12 | gold quality |
| prefrontal cortex | UBERON:0000451 | 89.96 | gold quality |
| left ventricle myocardium | UBERON:0006566 | 89.72 | gold quality |
| oviduct epithelium | UBERON:0004804 | 89.50 | gold quality |
| deltoid | UBERON:0001476 | 89.08 | silver quality |
| mucosa of sigmoid colon | UBERON:0004993 | 88.68 | gold quality |
| frontal cortex | UBERON:0001870 | 88.51 | gold quality |
| rectum | UBERON:0001052 | 88.28 | gold quality |
| bone marrow cell | CL:0002092 | 88.27 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 88.04 | gold quality |
| colonic mucosa | UBERON:0000317 | 87.94 | gold quality |
| parietal lobe | UBERON:0001872 | 87.94 | gold quality |
| neocortex | UBERON:0001950 | 87.90 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 87.74 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 87.63 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 87.58 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 87.55 | gold quality |
| primary visual cortex | UBERON:0002436 | 87.55 | gold quality |
| cerebellar cortex | UBERON:0002129 | 87.54 | gold quality |
| islet of Langerhans | UBERON:0000006 | 87.50 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 87.42 | gold quality |
| cerebral cortex | UBERON:0000956 | 87.37 | gold quality |
| corpus callosum | UBERON:0002336 | 87.25 | gold quality |
| monocyte | CL:0000576 | 87.09 | gold quality |
| entorhinal cortex | UBERON:0002728 | 87.06 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 87.06 | gold quality |
| leukocyte | CL:0000738 | 86.90 | gold quality |
| embryo | UBERON:0000922 | 86.80 | gold quality |
| ganglionic eminence | UBERON:0004023 | 86.80 | gold quality |
| cerebellum | UBERON:0002037 | 86.76 | gold quality |
| right frontal lobe | UBERON:0002810 | 86.61 | gold quality |
| ventricular zone | UBERON:0003053 | 86.45 | gold quality |
| corpus epididymis | UBERON:0004359 | 86.26 | gold quality |
| muscle of leg | UBERON:0001383 | 86.17 | gold quality |
| visceral pleura | UBERON:0002401 | 85.97 | gold quality |
| gastrocnemius | UBERON:0001388 | 85.83 | gold quality |
| right adrenal gland | UBERON:0001233 | 85.45 | gold quality |
| skin of hip | UBERON:0001554 | 85.45 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 85.39 | gold quality |
| muscle tissue | UBERON:0002385 | 85.28 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 85.18 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 85.17 | gold quality |
| forebrain | UBERON:0001890 | 85.11 | gold quality |
| brain | UBERON:0000955 | 84.98 | gold quality |
| biceps brachii | UBERON:0001507 | 84.95 | gold quality |
| occipital lobe | UBERON:0002021 | 84.95 | gold quality |
| adrenal gland | UBERON:0002369 | 84.95 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 84.94 | gold quality |
| cauda epididymis | UBERON:0004360 | 84.94 | gold quality |
| large intestine | UBERON:0000059 | 84.93 | gold quality |
| colon | UBERON:0001155 | 84.90 | gold quality |
| left adrenal gland | UBERON:0001234 | 84.90 | gold quality |
| Ammon's horn | UBERON:0001954 | 84.90 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 84.86 | gold quality |
| pancreas | UBERON:0001264 | 84.84 | gold quality |
| minor salivary gland | UBERON:0001830 | 84.80 | gold quality |
| quadriceps femoris | UBERON:0001377 | 84.78 | gold quality |
| lower esophagus | UBERON:0013473 | 84.72 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 84.72 | gold quality |
| intestine | UBERON:0000160 | 84.63 | gold quality |
| esophagus | UBERON:0001043 | 84.61 | gold quality |
| buccal mucosa cell | CL:0002336 | 84.60 | gold quality |
| vastus lateralis | UBERON:0001379 | 84.59 | gold quality |
| vagina | UBERON:0000996 | 84.57 | gold quality |
| popliteal artery | UBERON:0002250 | 84.57 | gold quality |
| tibial artery | UBERON:0007610 | 84.56 | gold quality |
| right coronary artery | UBERON:0001625 | 84.55 | gold quality |
| lymph node | UBERON:0000029 | 84.53 | gold quality |
| transverse colon | UBERON:0001157 | 84.51 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 84.48 | gold quality |
| esophagus mucosa | UBERON:0002469 | 84.46 | gold quality |
| endometrium | UBERON:0001295 | 84.43 | gold quality |
| left coronary artery | UBERON:0001626 | 84.38 | gold quality |
| parietal pleura | UBERON:0002400 | 84.36 | gold quality |
| decidua | UBERON:0002450 | 84.36 | gold quality |
| upper arm skin | UBERON:0004263 | 84.36 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 84.36 | gold quality |
| urinary bladder | UBERON:0001255 | 84.35 | gold quality |
| body of pancreas | UBERON:0001150 | 84.29 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 84.27 | gold quality |
| body of uterus | UBERON:0009853 | 84.25 | gold quality |
| gall bladder | UBERON:0002110 | 84.22 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 84.21 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 84.19 | gold quality |

#### Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

| Experiment | Marker? | Max mean expression |
| --- | --- | --- |
| [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/E-ANND-3) | no | 6.57 |

#### HPA expression

RNA tissue specificity: **Low tissue specificity**

showing 60 of 80 HPA tissues / cells by nTPM:

| Tissue / cell | Axis | nTPM | Protein (IHC) |
| --- | --- | --- | --- |
| Corpus callosum | tissue | 114.3 |  |
| Spinal cord | tissue | 91.9 |  |
| Medulla oblongata | tissue | 74.4 |  |
| Midbrain | tissue | 73.1 |  |
| Thalamus | tissue | 63.8 |  |
| Pons | tissue | 62.8 |  |
| Putamen | tissue | 57.3 |  |
| Substantia nigra | tissue | 57.2 |  |
| Superior colliculi | tissue | 56.4 |  |
| Hippocampal formation | tissue | 49.9 |  |
| Periaqueductal gray | tissue | 46.4 |  |
| Ventral forebrain | tissue | 45.8 |  |
| Cerebral cortex | tissue | 42.4 | medium |
| Somatosensory cortex | tissue | 42.4 |  |
| Septum | tissue | 41.9 |  |
| Occipital cortex | tissue | 41.6 |  |
| Motor cortex | tissue | 41.0 |  |
| Cerebellum | tissue | 40.0 | medium |
| Retrosplenial cortex | tissue | 39.9 |  |
| Hypothalamus | tissue | 39.1 |  |
| Retrosplenial and cingulate cortex | tissue | 38.0 |  |
| Entorhinal cortex | tissue | 37.4 |  |
| Prefrontal cortex | tissue | 36.7 |  |
| Temporal cortex | tissue | 35.2 |  |
| Basal ganglia | tissue | 34.7 | medium |
| Frontal cortex | tissue | 33.2 |  |
| Amygdala | tissue | 32.9 |  |
| Insular cortex | tissue | 32.5 |  |
| Olfactory bulb | tissue | 28.1 |  |
| Caudate putamen | tissue | 27.1 |  |
| Choroid plexus | tissue | 12.3 |  |
| Nucleus accumbens | tissue | 12.1 |  |
| Postcentral gyrus | tissue | 12.1 |  |
| Hippocampus | tissue | 11.3 | medium |
| Locus coeruleus | tissue | 9.3 |  |
| Breast | tissue | 6.6 | medium |
| Parathyroid gland | tissue | 5.6 | low |
| Rectum | tissue | 4.9 | medium |
| Skin 1 | tissue | 4.7 | medium |
| Retina | tissue | 4.7 |  |
| Tongue | tissue | 4.6 |  |
| Thyroid gland | tissue | 4.6 | medium |
| Kidney | tissue | 4.6 | medium |
| Lymph node | tissue | 4.5 | medium |
| Esophagus | tissue | 4.5 | medium |
| Placenta | tissue | 4.5 | medium |
| Tonsil | tissue | 4.4 | medium |
| Colon | tissue | 4.3 | medium |
| Endometrium 1 | tissue | 4.3 | medium |
| Spleen | tissue | 4.0 | low |
| Thymus | tissue | 4.0 |  |
| Epididymis | tissue | 3.9 | medium |
| Lung | tissue | 3.7 | medium |
| Salivary gland | tissue | 3.5 | medium |
| Testis | tissue | 3.4 | medium |
| Ovary | tissue | 3.4 | medium |
| Stomach 1 | tissue | 3.2 | medium |
| Smooth muscle | tissue | 3.2 | low |
| Pancreas | tissue | 3.2 | medium |
| Prostate | tissue | 3.2 | low |

**Brain sub-regions (HPA Brain Atlas):** detected in 192; highest nTPM — White matter (114.3), Ventral spinal cord (91.9), Dorsal spinal cord (75.9), Dorsal hippocampus (49.9), Ventral hippocampus (38.6).

### Regulation

**Is transcription factor: no**

#### miRNA regulators (miRDB)

Targeting VPS50 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 109 miRNAs:

| miRNA | Max score | Avg score | miRNA target_count |
| --- | --- | --- | --- |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-340-5P | 100.00 | 72.50 | 4437 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-4668-3P | 100.00 | 68.74 | 2635 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-4534 | 99.99 | 66.58 | 1907 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-5696 | 99.98 | 72.36 | 4487 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-548N | 99.98 | 71.94 | 4170 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-3605-5P | 99.96 | 67.12 | 932 |
| HSA-MIR-3658 | 99.96 | 73.87 | 4379 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
| HSA-MIR-5680 | 99.91 | 69.83 | 3421 |
| HSA-MIR-3529-3P | 99.90 | 73.55 | 3045 |
| HSA-MIR-3686 | 99.90 | 70.53 | 2432 |
| HSA-MIR-548E-5P | 99.89 | 72.73 | 4486 |
| HSA-MIR-153-5P | 99.89 | 73.86 | 6317 |
| HSA-MIR-548D-3P | 99.87 | 70.67 | 4362 |
| HSA-MIR-579-3P | 99.86 | 71.66 | 3628 |
| HSA-MIR-548BB-3P | 99.86 | 70.58 | 4354 |
| HSA-MIR-664B-3P | 99.84 | 71.65 | 3590 |
| HSA-MIR-548AC | 99.84 | 70.77 | 4351 |
| HSA-MIR-548H-3P | 99.84 | 70.80 | 4349 |
| HSA-MIR-548Z | 99.84 | 70.80 | 4349 |
| HSA-MIR-548AZ-5P | 99.83 | 69.94 | 3230 |
| HSA-MIR-548T-5P | 99.83 | 69.91 | 3220 |

### Functional genomics

**gnomAD constraint:** pLI 0.106, LOEUF 0.781, missense Z 1.21 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). [gnomAD](https://gnomad.broadinstitute.org/)

#### Regional missense constraint (gnomAD)

`ENST00000305866` splits into 3 regions with different missense tolerance; **0 are missense-constrained**. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. [gnomAD](https://gnomad.broadinstitute.org/)

| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
| --- | --- | --- | --- |
| 7:93,232,468–93,349,953 | 744 / 930.6 | 0.80 | no |
| 7:93,349,954–93,353,681 | 19 / 46.8 | 0.41 | no |
| 7:93,353,682–93,358,433 | 158 / 156.3 | 1.01 | no |

### Literature-anchored findings (GeneRIF, showing 1)

- Biallelic variants in VPS50 cause a neurodevelopmental disorder with neonatal cholestasis. (PMID:34037727)

### Cross-species orthologs

**6 orthologs**

| Organism | Symbol | Gene ID |
| --- | --- | --- |
| danio_rerio | vps50 | ENSDARG00000002880 |
| danio_rerio | vps50 | ENSDARG00000096912 |
| mus_musculus | Vps50 | ENSMUSG00000001376 |
| rattus_norvegicus | Vps50 | ENSRNOG00000009894 |
| drosophila_melanogaster | Vps50 | FBGN0034271 |
| caenorhabditis_elegans |  | WBGENE00008078 |

#### Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara's model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions' gene symbols aren't in biobtree yet, so each row shows the UniProt accession.

| Organism | UniProt | Identity | Method |
| --- | --- | --- | --- |
| Gallus gallus | [Q5ZKV9](https://www.uniprot.org/uniprotkb/Q5ZKV9/entry) | 89.5% | Diamond |

### Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

| Symbol | Type | Entrez |
| --- | --- | --- |
| [SAMD9L](/atlas/gene/SAMD9L/) | protein-coding | 219285 |
| [HEPACAM2](/atlas/gene/HEPACAM2/) | protein-coding | 253012 |
| [MIR489](/atlas/gene/MIR489/) | ncRNA | 574442 |
| [MIR653](/atlas/gene/MIR653/) | ncRNA | 724023 |
| [CALCR](/atlas/gene/CALCR/) | protein-coding | 799 |
| [SAMD9](/atlas/gene/SAMD9/) | protein-coding | 54809 |
| [MIR4652](/atlas/gene/MIR4652/) | ncRNA | 100616206 |

<a id="protein-Q96JG6"></a>

## Protein

### Protein identifiers

**Syndetin** — `Q96JG6` (reviewed: Q96JG6)

**Alternative names:** Coiled-coil domain-containing protein 132, EARP/GARPII complex subunit VPS50

**All UniProt accessions (8):** `A0A3B3IRQ5`, `B4DS55`, `C9JA29`, `Q96JG6`, `F2Z3F0`, `F8WDT1`, `H0Y7Q2`, `H7BZP1`

#### UniProt curated annotations — [full annotation on UniProt →](https://www.uniprot.org/uniprotkb/Q96JG6/entry)

**Function.** Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN).

**Subunit / interactions.** Component of the endosome-associated retrograde protein (EARP) complex, composed of VPS51, VPS52, VPS53 and VPS50/Syndetin. The EARP complex interacts with EIPR1. Interacts with VPS51 and VPS53 in an EIPR1-independent manner.

**Subcellular location.** Recycling endosome. Membrane.

**Tissue specificity.** Ubiquitous, with higher expression in brain and skeletal muscle.

**Disease relevance.** Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis (NEDMSC) [MIM:619685] An autosomal recessive disorder with onset at birth, characterized by severe global developmental delay, profoundly impaired intellectual development, progressive microcephaly, seizures, and transient neonatal cholestasis. Brain imaging shows agenesis or hypoplasia of the corpus callosum. Death in early childhood may occur. The disease may be caused by variants affecting the gene represented in this entry.

**Miscellaneous.** Was named 'syndetin' after the Greek 'syndeo', which means 'connect' or 'tether'.

**Similarity.** Belongs to the syndetin family.

#### Isoforms (3)

| UniProt ID | Names | Canonical? |
| --- | --- | --- |
| Q96JG6-1 | 1 | yes |
| Q96JG6-2 | 2 |  |
| Q96JG6-3 | 3 |  |

**RefSeq proteins (3):** `NP_001244927`, `NP_060137`*, `NP_078829`  (*=MANE)

#### Domains & families (InterPro)

| ID | Name | Type |
| --- | --- | --- |
| IPR019514 | Syndetin_C | Domain |
| IPR019515 | VPS54_N | Domain |
| IPR040047 | VPS50 | Family |

**Pfam:** `PF10474`, `PF10475`

**UniProt features (22 total):** modified residue 6, sequence conflict 4, splice variant 3, region of interest 2, cross-link 2, coiled-coil region 2, chain 1, sequence variant 1, compositionally biased region 1

### Structure

#### Predicted structure (AlphaFold)

| Model | pLDDT | Fraction very-high |
| --- | --- | --- |
| AF-Q96JG6-F1 | 71.19 | 0.10 |

### Human Protein Atlas

**Protein class:** Predicted intracellular proteins, Disease related genes

**Protein evidence:** Evidence at protein level

**Subcellular location (HPA, imaging):** cytosol; plasma membrane; basal body; end piece; mid piece; primary cilium; principal piece

**Antibody reliability (HPA):** IH approved · IF uncertain

### Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. *Source: UniProtKB sequence features.*

#### Post-translational modifications (8)

| Type | Positions |
| --- | --- |
| Phosphoserine | 559, 561, 15, 494, 498 |
| Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1) | 963 |
| Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2) | 963 |
| N-acetylmethionine | 1 |

## Function

### Pathways and Gene Ontology

#### Reactome pathways

**0 curated (TAS)** of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

**MSigDB gene sets: 221** (showing top):
`GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP`, `GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN`, `RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP`, `RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP`, `GOBP_VESICLE_MEDIATED_TRANSPORT`, `USF_C`, `PATIL_LIVER_CANCER`, `MODULE_239`, `GFI1_01`, `GOBP_ENDOCYTIC_RECYCLING`, `GOBP_RETROGRADE_TRANSPORT_ENDOSOME_TO_GOLGI`, `GOBP_LOCALIZATION_WITHIN_MEMBRANE`, `GOBP_CYTOSOLIC_TRANSPORT`, `GOCC_RECYCLING_ENDOSOME`, `VECCHI_GASTRIC_CANCER_EARLY_UP`

**GO Biological Process (3):**
protein transport (GO:0015031), endocytic recycling (GO:0032456), retrograde transport, endosome to Golgi (GO:0042147)

**GO Molecular Function (2):**
SNARE binding (GO:0000149), protein binding (GO:0005515)

**GO Cellular Component (6):**
membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), extracellular exosome (GO:0070062), EARP complex (GO:1990745), cytosol (GO:0005829)

#### GO top-level categories

14 GO namespaces:

| Category | Terms |
| --- | --- |
| cellular anatomical structure | 3 |
| endosomal transport | 2 |
| cytoplasm | 2 |
| transport | 1 |
| intracellular protein localization | 1 |
| establishment of protein localization | 1 |
| vesicle-mediated transport to the plasma membrane | 1 |
| cytosolic transport | 1 |
| protein binding | 1 |
| binding | 1 |
| endosome | 1 |
| extracellular vesicle | 1 |
| protein-containing complex | 1 |
| recycling endosome | 1 |

#### Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

| GO term | NS | Evidence |
| --- | --- | --- |
| [endocytic recycling](https://amigo.geneontology.org/amigo/term/GO:0032456) | BP | direct assay |
| [EARP complex](https://amigo.geneontology.org/amigo/term/GO:1990745) | CC | direct assay |
| [extracellular exosome](https://amigo.geneontology.org/amigo/term/GO:0070062) | CC | high-throughput assay |
| [membrane](https://amigo.geneontology.org/amigo/term/GO:0016020) | CC | high-throughput assay |
| [recycling endosome](https://amigo.geneontology.org/amigo/term/GO:0055037) | CC | direct assay |
| [SNARE binding](https://amigo.geneontology.org/amigo/term/GO:0000149) | MF | direct assay |

### Protein interactions and networks

#### STRING

showing 15 of 880 interactions by confidence (×1000):

| Protein A | Protein B | Partner UniProt | Score |
| --- | --- | --- | --- |
| VPS50 | VPS53 | Q5VIR6 | 814 |
| VPS50 | VPS54 | Q9P1Q0 | 813 |
| VPS50 | VPS51 | Q9UID3 | 789 |
| VPS50 | VPS52 | Q8N1B4 | 774 |
| VPS50 | HEPACAM2 | A8MVW5 | 632 |
| VPS50 | CCDC186 | Q7Z3E2 | 632 |
| VPS50 | EIPR1 | Q53HC9 | 625 |
| VPS50 | CCDC138 | Q96M89 | 499 |
| VPS50 | RUNDC1 | Q96C34 | 483 |
| VPS50 | ARL5A | Q9Y689 | 474 |
| VPS50 | RBM26 | Q5T8P6 | 468 |
| VPS50 | ARFRP1 | Q13795 | 462 |
| VPS50 | PCED1A | Q9H1Q7 | 460 |
| VPS50 | STX6 | O43752 | 450 |
| VPS50 | DYM | Q7RTS9 | 445 |

#### IntAct

Human interaction partners of VPS50 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 33 partners by confidence:

| Partner | Interaction type | MIscore | Records |
| --- | --- | --- | --- |
| VPS53 | physical association | 0.840 | 4 |
| VPS52 | physical association | 0.830 | 2 |
| VPS51 | physical association | 0.640 | 3 |
| CTNNBL1 | physical association | 0.400 | 1 |
| BMAL1 | physical association | 0.000 | 1 |
| CAVIN1 | physical association | 0.000 | 1 |
| CCDC93 | physical association | 0.000 | 1 |
| CCHCR1 | physical association | 0.000 | 1 |
| CLOCK | physical association | 0.000 | 1 |
| DZIP3 | physical association | 0.000 | 1 |
| EIPR1 | physical association | 0.000 | 1 |
| GIT2 | physical association | 0.000 | 1 |
| GOLGA5 | physical association | 0.000 | 1 |
| GRIPAP1 | physical association | 0.000 | 1 |
| HAUS6 | physical association | 0.000 | 1 |
| HMG20A | physical association | 0.000 | 1 |
| KDM1A | physical association | 0.000 | 1 |
| MAX | physical association | 0.000 | 1 |
| NCKAP5L | physical association | 0.000 | 1 |
| NUF2 | physical association | 0.000 | 1 |
| OIP5 | physical association | 0.000 | 1 |
| PHF21A | physical association | 0.000 | 1 |
| PHLDB3 | physical association | 0.000 | 1 |
| PKN3 | physical association | 0.000 | 1 |
| PSMD9 | physical association | 0.000 | 1 |
| RABGAP1L | physical association | 0.000 | 1 |
| RABGEF1 | physical association | 0.000 | 1 |
| RCOR1 | physical association | 0.000 | 1 |
| RPRD1A | physical association | 0.000 | 1 |
| TFPT | physical association | 0.000 | 1 |

#### Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexe by size:

| Complex | Subunits | Members |
| --- | --- | --- |
| EARP complex | 4 | VPS50, VPS51, VPS52, VPS53 |

#### Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene's 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — *distinct from this gene's own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.*

**GO biological processes:**

| GO term | Partners | Fold | FDR |
| --- | --- | --- | --- |
| endocytic recycling | 5 | 41.8× | 1e-05 |
| protein transport | 6 | 8.2× | 2e-03 |

## Disease & clinical

### Genetic variants

**Variant evidence for VPS50:** [160 ClinVar records](#clinvar) (9 pathogenic / likely pathogenic); [1 GWAS association](#gwas-assoc). Per-variant detail is on [Sugi Variant](https://sugi.bio/variant/gene/VPS50).

#### ClinVar

160 variants total. Per-class counts are floors (≥ shown; pagination cap):

| Classification | Count (floor) |
| --- | --- |
| Pathogenic | 4 |
| Likely pathogenic | 5 |
| Uncertain significance | 90 |
| Likely benign | 14 |
| Benign | 2 |

#### Top pathogenic / likely-pathogenic (9)

Showing all 9 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

| Variant ID | HGVS | Classification | Review | Submitters |
| --- | --- | --- | --- | --- |
| 3064458 | [NM_017667.4(VPS50):c.1705C>T (p.Arg569Ter)](https://sugi.bio/variant/vps50-p-arg569ter) | Likely pathogenic | criteria provided, single submitter | 1 |
| 3235924 | [NM_017667.4(VPS50):c.1723C>T (p.Gln575Ter)](https://sugi.bio/variant/vps50-p-gln575ter) | Likely pathogenic | criteria provided, single submitter | 1 |
| 3388705 | [NM_017667.4(VPS50):c.2464-1G>C](https://sugi.bio/variant/vps50-c-2464-minus-1g-c) | Likely pathogenic | criteria provided, single submitter | 1 |
| 3388706 | [NM_017667.4(VPS50):c.2208-2A>G](https://sugi.bio/variant/vps50-c-2208-minus-2a-g) | Likely pathogenic | criteria provided, single submitter | 1 |
| 4535162 | [NM_017667.4(VPS50):c.1739del (p.Pro580fs)](https://sugi.bio/variant/vps50-p-pro580fs) | Likely pathogenic | criteria provided, single submitter | 1 |
| 1331700 | [NM_017667.4(VPS50):c.1978-1G>T](https://sugi.bio/variant/vps50-c-1978-minus-1g-t) | Pathogenic | no assertion criteria provided | 1 |
| 1331701 | [NM_017667.4(VPS50):c.1823_1825del (p.Thr608del)](https://sugi.bio/variant/vps50-p-thr608del) | Pathogenic | no assertion criteria provided | 1 |
| 4853803 | [NM_017667.4(VPS50):c.13A>T (p.Lys5Ter)](https://sugi.bio/variant/vps50-p-lys5ter) | Pathogenic | no assertion criteria provided | 1 |
| 4853804 | VPS50, GENE DELETION, 428-KB | Pathogenic | no assertion criteria provided | 1 |

#### Per-variant reference — Sugi Variant

Explore VPS50's pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on [Sugi Variant](https://sugi.bio/variant/gene/VPS50).

#### SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 2,676):

| Position(s) | Effect | Δscore | Sites |
| --- | --- | --- | --- |
| 7:93253843 | acceptor_gain | 1.0000 |  |
| 7:93256507–93256508 | acceptor_loss | 1.0000 | 4 |
| 7:93256563–93256564 | donor_loss | 1.0000 | 6 |
| 7:93258393–93258394 | donor_loss | 1.0000 | 5 |
| 7:93259633–93259634 | donor_loss | 1.0000 | 5 |
| 7:93271263–93271264 | donor_loss | 1.0000 | 4 |
| 7:93272626–93272627 | acceptor_gain | 1.0000 | 2 |
| 7:93272630–93272632 | acceptor_gain | 1.0000 | 2 |
| 7:93272633–93272634 | acceptor_loss | 1.0000 | 4 |
| 7:93272734–93272735 | donor_loss | 1.0000 | 5 |

#### AlphaMissense

3,018 missense substitutions predicted likely pathogenic (of 6,390 scored), across 685 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
| --- | --- | --- | --- |
| M877 | 9 | 0.985 | 1.000 |
| M275 | 9 | 0.947 | 0.999 |
| M624 | 9 | 0.889 | 0.992 |
| M462 | 9 | 0.871 | 0.995 |
| D880 | 8 | 0.999 | 1.000 |
| D238 | 8 | 0.997 | 0.999 |
| H453 | 8 | 0.993 | 0.999 |
| D271 | 8 | 0.989 | 0.996 |
| H812 | 8 | 0.988 | 0.998 |
| H276 | 8 | 0.983 | 0.998 |
| D228 | 8 | 0.982 | 0.998 |
| F463 | 8 | 0.982 | 1.000 |
| F524 | 8 | 0.979 | 0.997 |
| F654 | 8 | 0.976 | 0.997 |
| F478 | 8 | 0.971 | 0.997 |
| D644 | 8 | 0.970 | 0.996 |
| D184 | 8 | 0.959 | 0.992 |
| F429 | 8 | 0.958 | 0.998 |
| D327 | 8 | 0.957 | 0.983 |
| N466 | 8 | 0.952 | 0.996 |

### HPA cancer prognostics

**RNA cancer specificity:** Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

| Cancer | Prognostic | p-value |
| --- | --- | --- |
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 2.03e-06 |
| Colon Adenocarcinoma (TCGA) | unfavorable | 0.000608 |

### Disease associations

**OMIM:** gene `MIM:616465` | disease phenotypes: MIM:619685 (Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis)

#### GenCC curated gene-disease

1 curated gene-disease records:

| Disease | Classification | Inheritance | Records |
| --- | --- | --- | --- |
| [neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis](/atlas/disease/neurodevelopmental-disorder-with-microcephaly-seizures-and-neonatal-cholestasis/) | Strong | Autosomal recessive | 2 |

#### Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

| Panel | Rating |
| --- | --- |
| Fetal anomalies | green |
| Cerebral malformation | amber |
| Cholestasis | amber |
| Early onset or syndromic epilepsy | amber |
| Hypotonic infant | amber |
| Intellectual disability | amber |
| Leukodystrophy, childhood onset | amber |
| Malformations of cortical development | amber |
| Paediatric disorders | amber |
| Severe microcephaly | amber |
| Unexplained death in infancy and sudden unexplained death in childhood | amber |

**Mondo (1):** [neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis](/atlas/disease/neurodevelopmental-disorder-with-microcephaly-seizures-and-neonatal-cholestasis/) (MONDO:0859216)

#### HPO phenotypes

22 phenotypes (HPO-id order):

| HPO | Term |
| --- | --- |
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000737 | Irritability |
| HP:0001272 | Cerebellar atrophy |
| HP:0001406 | Intrahepatic cholestasis |
| HP:0002079 | Hypoplasia of the corpus callosum |
| HP:0002179 | Opisthotonus |
| HP:0002421 | Poor head control |
| HP:0002904 | Hyperbilirubinemia |
| HP:0003623 | Neonatal onset |
| HP:0003819 | Death in childhood |
| HP:0005484 | Secondary microcephaly |
| HP:0008689 | Bilateral cryptorchidism |
| HP:0010818 | Generalized tonic seizure |
| HP:0011003 | High myopia |
| HP:0011344 | Severe global developmental delay |
| HP:0011968 | Feeding difficulties |
| HP:0012202 | Increased serum bile acid concentration |
| HP:0012595 | Mild proteinuria |
| HP:0020045 | Esodeviation |
| HP:0031956 | Elevated circulating aspartate aminotransferase concentration |
| HP:0031964 | Elevated circulating alanine aminotransferase concentration |
| HP:0040288 | Nasogastric tube feeding |

#### GWAS associations

1 association:

| Study | Trait | p-value |
| --- | --- | --- |
| GCST009153_6 | Adverse response to chemotherapy (amenorrhea) in breast cancer | 8e-7 |

## Drugs & pharmacology

### Drug and pharmacology data

**Is drug target: no**

**PharmGKB:** 1 entry (CPIC guideline: no)

#### CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

| Chemical | Actions (top 5) | PubMed papers |
| --- | --- | --- |
| trichostatin A | affects cotreatment, decreases expression | 3 |
| Valproic Acid | increases expression, decreases expression | 2 |
| Cadmium Chloride | decreases reaction, increases abundance, increases palmitoylation, increases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| FR900359 | affects phosphorylation | 1 |
| bisphenol F | increases expression | 1 |
| TAK-243 | decreases sumoylation | 1 |
| dicrotophos | decreases expression | 1 |
| geldanamycin | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| sodium arsenite | decreases expression | 1 |
| 2-bromopalmitate | increases palmitoylation, decreases reaction, increases abundance | 1 |
| ochratoxin A | decreases expression | 1 |
| potassium chromate(VI) | affects cotreatment, decreases expression | 1 |
| coumarin | increases phosphorylation | 1 |
| epigallocatechin gallate | affects cotreatment, decreases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| perfluorooctane sulfonic acid | decreases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 1 |
| bisphenol B | increases expression | 1 |
| abrine | decreases expression | 1 |
| dorsomorphin | affects cotreatment, decreases expression | 1 |
| jinfukang | decreases expression | 1 |
| Resveratrol | affects cotreatment, increases expression | 1 |
| Sunitinib | decreases expression | 1 |
| Acetaminophen | decreases expression | 1 |
| Air Pollutants | decreases expression, increases abundance | 1 |
| Benzo(a)pyrene | decreases expression | 1 |
| Cadmium | decreases reaction, increases abundance, increases palmitoylation | 1 |
| Caffeine | affects phosphorylation | 1 |

#### Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

| Cellosaurus | Name | Category | Sex |
| --- | --- | --- | --- |
| CVCL_SH19 | HAP1 CCDC132 (-) | Cancer cell line | Male |

#### Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

## Related Atlas pages

- **Associated diseases:** [neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis](/atlas/disease/neurodevelopmental-disorder-with-microcephaly-seizures-and-neonatal-cholestasis/)
- **Disease cohort memberships** *(association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases)*: [amenorrhea](/atlas/disease/amenorrhea/), [neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis](/atlas/disease/neurodevelopmental-disorder-with-microcephaly-seizures-and-neonatal-cholestasis/)