KRT74

keratin 74, the group of Keratins, type II

Basic information

Region (hg38): 12:52565781-52573843

Links

ENSG00000170484 ∙ NCBI:121391 ∙ OMIM:608248 ∙ HGNC:28929 ∙ Uniprot:Q7RTS7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotrichosis 3 (Strong), mode of inheritance: AD
• isolated familial wooly hair disorder (Supportive), mode of inheritance: AD
• pure hair and nail ectodermal dysplasia (Supportive), mode of inheritance: AD
• hypotrichosis simplex of the scalp (Supportive), mode of inheritance: AD
• autosomal dominant wooly hair (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 7, hair/nail type; Hypotrichosis 3; Woolly hair, autosomal dominant	AD	General	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	Dermatologic	20346438; 20409997; 21188418; 24714551

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT74 gene.

• not provided (101 variants)
• Inborn genetic diseases (38 variants)
• Ectodermal dysplasia 7, hair/nail type (1 variants)
• Ectodermal dysplasia 4, hair/nail type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT74 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	15	20
missense			45	9	20	74
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)					1	1
splice region			2		1	3
non coding				2	33	35
Total	0	0	45	16	69

Variants in KRT74

This is a list of pathogenic ClinVar variants found in the KRT74 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-52567001-C-T		not specified	Uncertain significance (Mar 28, 2022)
12-52567006-G-T			Uncertain significance (Apr 25, 2022)
12-52567025-C-T		KRT74-related disorder	Uncertain significance (Feb 09, 2024)
12-52567035-TC-T			Uncertain significance (Dec 02, 2022)
12-52567037-C-T		not specified	Uncertain significance (Jan 04, 2024)
12-52567039-C-A			Likely benign (Sep 12, 2023)
12-52567044-C-A		KRT74-related disorder	Benign/Likely benign (Nov 24, 2023)
12-52567045-G-A		not specified	Likely benign (Jul 03, 2023)
12-52567052-T-C			Benign (Jan 29, 2024)
12-52567068-G-A		KRT74-related disorder	Benign/Likely benign (Mar 19, 2022)
12-52567089-G-A		KRT74-related disorder	Likely benign (Feb 07, 2024)
12-52567100-C-T			Benign (Jan 05, 2024)
12-52567115-C-T		Hypotrichosis 3	Pathogenic (Apr 01, 2011)
12-52567133-G-A		KRT74-related disorder	Benign (Nov 16, 2023)
12-52567142-A-G		not specified	Uncertain significance (Feb 28, 2024)
12-52567150-C-A		not specified	Uncertain significance (Dec 05, 2022)
12-52567169-C-T		Autosomal dominant wooly hair	Pathogenic (Apr 01, 2011)
12-52567186-A-G			Benign (Feb 13, 2023)
12-52567369-C-A			Benign (Nov 12, 2018)
12-52567370-A-G			Benign (Nov 12, 2018)
12-52567433-C-G			Benign (Jun 19, 2021)
12-52567521-A-T			Benign (Jun 21, 2021)
12-52567534-C-T			Benign (Jun 20, 2021)
12-52567641-T-C			Likely benign (Feb 27, 2023)
12-52567650-A-T			Likely benign (Dec 11, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT74	protein_coding	protein_coding	ENST00000305620	9	8044

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.12e-14	0.00853	125329	2	417	125748	0.00167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.20	363	304	1.19	0.0000198	3452
Missense in Polyphen		93	79.496	1.1699		1144
Synonymous	-1.66	152	128	1.19	0.00000827	1066
Loss of Function	-0.371	20	18.3	1.09	8.05e-7	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00672	0.00660
Ashkenazi Jewish	0.0102	0.0103
East Asian	0.00228	0.00229
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000906	0.000897
Middle Eastern	0.00228	0.00229
South Asian	0.0000980	0.0000980
Other	0.00309	0.00294

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (Probable). {ECO:0000305}.
• Disease: DISEASE: Hypotrichosis 3 (HYPT3) [MIM:613981]: A condition characterized by the presence of less than the normal amount of hair. Affected individuals have normal hair in early childhood but experience progressive hair loss limited to the scalp beginning in the middle of the first decade and almost complete baldness by the third decade. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. {ECO:0000269|PubMed:21188418}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ectodermal dysplasia 7, hair/nail type (ECTD7) [MIM:614929]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. Ectodermal dysplasia of the hair/nail type is characterized by hypotrichosis and nail dystrophy without non- ectodermal or other ectodermal manifestations. {ECO:0000269|PubMed:24714551}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Keratinization;Developmental Biology (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.147
• rvis_EVS: 2.38
• rvis_percentile_EVS: 98.48

Haploinsufficiency Scores

• pHI: 0.148
• hipred: N
• hipred_score: 0.146
• ghis: 0.430

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.664

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt74

Gene ontology

• Biological process: keratinization;intermediate filament cytoskeleton organization;cornification
• Cellular component: cytoplasm;cytosol;keratin filament;extracellular exosome
• Molecular function: structural molecule activity;keratin filament binding