KDF1

keratinocyte differentiation factor 1

Basic information

Region (hg38): 1:26949562-26960468

Previous symbols: [ "C1orf172" ]

Links

ENSG00000175707 ∙ NCBI:126695 ∙ OMIM:616758 ∙ HGNC:26624 ∙ Uniprot:Q8NAX2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AD
• ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type (Moderate), mode of inheritance: AD
• ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Craniofacial; Dental; Dermatologic	27838789

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDF1 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				10	3	13
missense		1	43	3	6	53
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	1	2
Total	0	1	44	14	10

Variants in KDF1

This is a list of pathogenic ClinVar variants found in the KDF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-26950095-C-A		Inborn genetic diseases	Uncertain significance (Sep 19, 2022)
1-26950099-C-T		KDF1-related disorder	Benign (Jan 29, 2024)
1-26950101-A-G			Uncertain significance (Apr 26, 2023)
1-26950103-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
1-26950113-C-T			Benign/Likely benign (Sep 01, 2024)
1-26950128-A-G		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
1-26950668-G-A			Likely benign (Oct 04, 2023)
1-26950669-G-T			Benign (Dec 23, 2022)
1-26950708-C-T		Inborn genetic diseases	Uncertain significance (Aug 28, 2024)
1-26950729-G-A		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
1-26950740-G-A			Likely benign (Jun 26, 2018)
1-26950762-G-A		KDF1-related disorder	Benign (Nov 16, 2023)
1-26951368-A-G		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
1-26951416-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
1-26951425-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 13, 2023)
1-26951461-C-G		Partial congenital absence of teeth	Uncertain significance (-)
1-26951471-T-C			Uncertain significance (Oct 20, 2023)
1-26951484-G-A		KDF1-related disorder	Likely benign (Aug 29, 2019)
1-26951494-C-CGGCCCTCAGCATCCTGCTCATCCAGGT			Uncertain significance (May 19, 2022)
1-26951532-C-T		KDF1-related disorder	Benign (Jan 24, 2024)
1-26951533-G-A		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
1-26951536-A-C			Uncertain significance (Jan 18, 2024)
1-26951628-G-T		Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type	Pathogenic (Feb 06, 2017)
1-26951632-A-G			Uncertain significance (Nov 01, 2021)
1-26951654-T-G		Partial congenital absence of teeth	Likely pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDF1	protein_coding	protein_coding	ENST00000320567	3	10845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.154	0.843	125735	0	6	125741	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.897	225	266	0.845	0.0000174	2553
Missense in Polyphen		86	121.88	0.70563		1201
Synonymous	0.125	102	104	0.984	0.00000606	857
Loss of Function	2.58	4	14.6	0.273	9.62e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000651	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000447	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the regulation of the epidermis formation during early development. Required both as an inhibitor of basal cell proliferation and a promoter of differentiation of basal progenitor cell progeny (By similarity). {ECO:0000250|UniProtKB:A2A9F4}.
• Disease: DISEASE: Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type (ECTD12) [MIM:617337]: A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD12 is an autosomal dominant, hypohidrotic form characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth, and the inability to sweat due to defective development of sweat glands. {ECO:0000269|PubMed:27838789}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.78

Haploinsufficiency Scores

• pHI: 0.661
• hipred: N
• hipred_score: 0.387
• ghis: 0.508

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Kdf1
• Phenotype: digestive/alimentary phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: keratinocyte development;regulation of epidermal cell division;negative regulation of keratinocyte proliferation;morphogenesis of embryonic epithelium;positive regulation of epidermal cell differentiation;developmental growth;limb epidermis development;establishment of skin barrier;negative regulation of stem cell proliferation
• Cellular component: nucleoplasm;cytoplasm;cell cortex;cell junction;cell leading edge;mitotic spindle