KHDC4

Chr 1

KH domain containing 4, pre-mRNA splicing factor

Also known as: BLOM7, KIAA0907, SNORA80EHG

NCBI Gene: 22889 ENSG00000132680 UniProt: Q7Z7F0 OMIM: 619370

Enables RNA binding activity. Involved in mRNA splice site recognition. Located in cytoplasm; nucleoplasm; and spliceosomal complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Enables RNA binding activity. Involved in mRNA splice site recognition. Located in cytoplasm; nucleoplasm; and spliceosomal complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.32

Clinical Summary— KHDC4

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

74 VUS of 103 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.969

Z-score 4.50

OE 0.15 (0.08–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.74Z-score

OE missense 0.73 (0.66–0.81)

241 obs / 330.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.32)

0≤0.351.4

Missense OE?0.73 (0.66–0.81)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 5 / 32.8Missense obs/exp: 241 / 330.2Syn Z: 0.73

This gene — mechanism propensity

0.3694th %ile

GOF

0.3986th %ile

LOF

0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS74

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	74	0	0	74
Likely Benign	0	0	1	1
Benign	0	1	0	1
Total	74	1	1	76

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap KHDC4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →