KRT4

Chr 12

keratin 4

ENSG00000170477 UniProt: P19013

Structural component of intermediate filaments in mucosal stratified squamous epithelia. Forms heteropolymers with the type I keratin KRT13, assembling into keratin intermediate filament networks that provides structural integrity and mechanical stability of the mucosal epithelium

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWhite sponge nevus 1

Clinical highlights

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

DN*

Mechanism· G2P

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.000

Z-score 1.33

OE 0.71 (0.49–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.46Z-score

OE missense 1.08 (0.98–1.18)

314 obs / 292.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.71 (0.49–1.06)

0≤0.351.4

Missense OE?1.08 (0.98–1.18)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 18 / 25.2Missense obs/exp: 314 / 292.1Syn Z: -1.10

Background carrier burden — how many people carry a rare variant somewhere in KRT4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

707 rare PASS variants

Rare truncating (LoF)

1 in 570

98 rare PASS variants

Rare synonymous (reference)

1 in 110

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KRT4. 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 72	1 in 1,100
South Asian	~43k	1 in 53	1 in 640
Remaining (unassigned)	~30k	1 in 63	1 in 600
European (Finnish)	~27k	1 in 400	≈ 1 in 8,900
Admixed American	~22k	1 in 54	1 in 1,100
African / African American	~21k	1 in 59	1 in 950
East Asian	~20k	1 in 68	1 in 410
Ashkenazi Jewish	~13k	1 in 600	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 73	1 in 450

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): 9 of 9 coding exons well covered in gnomAD exomes. Genomes: 8 of 9 (exon 1 below).? see exons ↓