KHDRBS3

Chr 8

KH RNA binding domain containing, signal transduction associated 3

Also known as: Etle, SALP, SLM-2, SLM2, T-STAR, TSTAR, etoile

The KHDRBS3 protein binds RNA and regulates alternative mRNA splicing, particularly of neurexins which are critical for synaptic function and targeting. Mutations cause autosomal recessive intellectual disability with variable features including developmental delay and neurological abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.493), and its regulation of neurexin splicing at glutamatergic synapses explains the neurodevelopmental phenotype.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
11
Pubs (1 yr)
54
P/LP submissions
0%
P/LP missense
0.49
LOEUF
Mechanism
Clinical SummaryKHDRBS3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 46 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.442
Z-score 3.13
OE 0.22 (0.100.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.32Z-score
OE missense 0.73 (0.630.84)
136 obs / 186.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.100.49)
00.351.4
Missense OE0.73 (0.630.84)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 4 / 18.6Missense obs/exp: 136 / 186.7Syn Z: 0.09

ClinVar Variant Classifications

117 submitted variants in ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic1
VUS46
Likely Benign3
53
Pathogenic
1
Likely Pathogenic
46
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
1
0
1
VUS
0
41
5
0
46
Likely Benign
0
0
3
0
3
Benign
0
0
0
0
0
Total041620103

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

View in ClinVar →

Protein Context — Lollipop Plot

KHDRBS3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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