KRT12

protein-coding

keratin 12, the group of Keratins, type I

Gene summary

KRT12 encodes the type I intermediate filament chain keratin 12, expressed in corneal epithelia. Mutations in this gene lead to Meesmann corneal dystrophy. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000223.4

Inheritance

ClinVar variants

P:11U:69B:21

Top phenotype

Meesmann corneal dystrophy 1

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr17:40,861,303-40,867,223

External References & Databases

Ensembl (ENSG00000187242)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

corneal dystrophy, Meesmann, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020791

Submitter: Labcorp Genetics (formerly Invitae)

corneal dystrophy, Meesmann, 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020791

Submitter: G2P

Meesmann corneal dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007379

Submitter: Orphanet

corneal dystrophy, Meesmann, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020791

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Meesmann corneal dystrophy 1AD

Manifestation: Ophthalmologic

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: 9171831; 18661274; 20577595

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT12 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 52

not providedTotal: 51

Corneal dystrophy, Meesmann, 1Total: 14

KRT12-related disorderTotal: 6

not specifiedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000223.4. 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				5 clinvar	3 clinvar	8
missense	8 clinvar	3 clinvar	63 clinvar	9 clinvar	4 clinvar	87
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	8	3	69	14	7	101

Highest pathogenic variant AF is 0.000026643898

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000223.4	RefSeq	NP_000214.1	8	MANE Select
ENST00000251643.5	Ensembl	ENSP00000251643.4	8	MANE Select
ENST00000647902.1	Ensembl	ENSP00000497770.1	4	Standard
ENST00001142097.1	Ensembl	ENSP00000802572.1	8	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

visual perception
keratinization
cornification

Molecular Function

structural molecule activity

Cellular Component

cytosol
intermediate filament
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251643
Coding exons: 8
Length: 5908
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125748
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.570	266	293	0.906	0.0000182	3187
Missense (PolyPhen)		92	108.08	0.85124		1282
Synonymous	1.36	108	127	0.847	0.00000861	1034
Loss of Function	0.346	22	23.8	0.923	0.00000136	253

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00030	0.00029	rare
South Asian	0.00020	0.00020	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a unique role in maintaining the normal corneal epithelial function. Together with KRT3, essential for the maintenance of corneal epithelium integrity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.215

Intolerance Scores

LoFtool: 0.199
RVIS EVS: 0.51
RVIS percentile EVS: 80.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.645

Gene Damage Prediction

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