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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in KHDC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

718 rare PASS variants

Rare truncating (LoF)

1 in 950

53 rare PASS variants

Rare synonymous (reference)

1 in 230

264 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KHDC4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 940
South Asian	~43k	1 in 130	1 in 960
Remaining (unassigned)	~30k	1 in 140	1 in 1,000
European (Finnish)	~27k	1 in 470	1 in 590
Admixed American	~22k	1 in 150	1 in 590
African / African American	~21k	1 in 110	1 in 2,400
East Asian	~20k	1 in 190	1 in 2,400
Ashkenazi Jewish	~13k	1 in 1,600	1 in 1,100
Middle Eastern	~2,884	1 in 160	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 14 coding exons well covered in gnomAD exomes; exons 9, 13 marginal. Genomes: 13 of 14 (exon 11 below).? see exons ↓