KRT25

protein-coding

keratin 25, the group of Keratins, type I

Gene summary

This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2009]

Previous symbols:

KRT25A

MANE transcript

NM_181534.4

Inheritance

AD, AR

ClinVar variants

P:2U:74B:25

Top phenotype

Woolly hair, autosomal recessive 3

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr17:40,748,021-40,755,331

External References & Databases

Ensembl (ENSG00000204897)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated familial wooly hair disorderSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008686

Submitter: Orphanet

wooly hair, autosomal recessive 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014765

Submitter: Labcorp Genetics (formerly Invitae)

wooly hair, autosomal recessive 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014765

Submitter: PanelApp Australia

wooly hair, autosomal recessive 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014765

Submitter: G2P

wooly hair, autosomal recessive 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014765

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Woolly hair, autosomal recessive 3AR

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26160856

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT25 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 38

Wooly hair, autosomal recessive 3Total: 3

KRT25-related disorderTotal: 3

Hypotrichosis 8Total: 1

Autosomal Recessive Hypotrichosis with Woolly HairTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181534.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				11 clinvar	3 clinvar	14
missense	2 clinvar		74 clinvar	8 clinvar	3 clinvar	87
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	74	19	6	101

Highest pathogenic variant AF is 0.000021064867

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181534.4	RefSeq	NP_853512.1	8	MANE Select
ENST00000312150.5	Ensembl	ENSP00000310573.4	8	MANE Select
XM_011524414.2	RefSeq	XP_011522716.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Estrogen signaling pathway - Homo sapiens (human)
Keratinization
Developmental Biology

Biological Process

cytoskeleton organization
aging
hair follicle morphogenesis
keratinization
hair cycle

Molecular Function

molecular_function
structural molecule activity
protein heterodimerization activity

Cellular Component

cytosol
intermediate filament
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000312150
Coding exons: 8
Length: 7312
Individuals with no LoFs: 125687
Homozygous LoFs: 0
Heterozygous LoFs: 61
Defined: 125748
p: 0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.166	248	255	0.971	0.0000142	2928
Missense (PolyPhen)		91	98.38	0.92499		1183
Synonymous	0.143	101	103	0.982	0.00000618	903
Loss of Function	1.21	16	22.2	0.722	0.00000119	252

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00021	rare
South Asian	0.00037	0.00036	rare
Other	0.00084	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for the proper assembly of type I and type II keratin protein complexes and formation of keratin intermediate filaments in the inner root sheath (irs) (By similarity). Plays a role in the cytoskeleton organization (PubMed:26902920). {ECO:0000250|UniProtKB:Q8VCW2, ECO:0000269|PubMed:26902920}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.267
RVIS EVS: 0.15
RVIS percentile EVS: 64.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0616

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium