CYTH3

Chr 7

cytohesin 3

Also known as: ARNO3, GRP1, PSCD3, cytohesin-3

NCBI Gene: 9265 ENSG00000008256 UniProt: O43739 OMIM: 605081

The protein functions as a guanine-nucleotide exchange factor that activates ARF1 and ARF6 by promoting GDP to GTP exchange, controlling Golgi structure and function, protein sorting, and membrane trafficking. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delays. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.42), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the PSCD (pleckstrin homology, Sec7 and coiled-coil domains) family. PSCD family members have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This encoded protein is involved in the control of Golgi structure and function, and it may have a physiological role in regulating ADP-ribosylation factor protein 6 (ARF) functions, in addition to acting on ARF1. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.42

Clinical Summary— CYTH3

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.

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ClinVar Variants

33 VUS of 48 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.723

Z-score 3.53

OE 0.18 (0.09–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.57Z-score

OE missense 0.54 (0.47–0.62)

133 obs / 246.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.18 (0.09–0.42)

0≤0.351.4

Missense OE?0.54 (0.47–0.62)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 4 / 21.7Missense obs/exp: 133 / 246.5Syn Z: -2.15

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	33	33
Likely Benign	0	0
Benign	0	0
Total	33	33

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap CYTH3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →