HOXC13

homeobox C13, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 12:53938830-53946544

Previous symbols: [ "HOX3", "HOX3G" ]

Links

ENSG00000123364 ∙ NCBI:3229 ∙ OMIM:142976 ∙ HGNC:5125 ∙ Uniprot:P31276 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ectodermal dysplasia 9, hair/nail type (Definitive), mode of inheritance: AR
• ectodermal dysplasia 9, hair/nail type (Strong), mode of inheritance: AR
• pure hair and nail ectodermal dysplasia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 9	AR	General	Males have been described as being affected with genitourinary anomalies, some of which require interventions; 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	23063621

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXC13 gene.

• Inborn genetic diseases (20 variants)
• not provided (11 variants)
• Ectodermal dysplasia 9, hair/nail type (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXC13 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				2		2
missense			25	1	1	27
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	2	0	25	4	3

Highest pathogenic variant AF is 0.0000329

Variants in HOXC13

This is a list of pathogenic ClinVar variants found in the HOXC13 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-53938949-C-CTTA			Benign (Jan 25, 2024)
12-53938959-T-C		not specified	Uncertain significance (Jan 10, 2023)
12-53938967-G-A			Likely benign (Jul 10, 2023)
12-53938989-T-TCGG		HOXC13-related disorder	Likely benign (May 25, 2022)
12-53938997-G-A		not specified	Uncertain significance (Jan 20, 2023)
12-53939006-G-A		not specified	Uncertain significance (Apr 07, 2022)
12-53939010-G-A		not specified	Uncertain significance (Feb 14, 2024)
12-53939018-G-A			Uncertain significance (Apr 26, 2022)
12-53939019-G-A		not specified	Uncertain significance (Oct 27, 2023)
12-53939031-C-CG			Pathogenic (Nov 12, 2022)
12-53939142-G-C		not specified	Uncertain significance (Jan 29, 2024)
12-53939166-C-T			Uncertain significance (Jan 20, 2020)
12-53939171-C-G		not specified	Uncertain significance (Feb 16, 2023)
12-53939178-C-T		not specified	Uncertain significance (Feb 23, 2023)
12-53939186-A-G		HOXC13-related disorder	Uncertain significance (Jan 11, 2024)
12-53939187-C-A			Benign (Aug 10, 2023)
12-53939208-C-T		not specified	Uncertain significance (Oct 12, 2021)
12-53939231-C-T		Ectodermal dysplasia 9, hair/nail type	Uncertain significance (Oct 28, 2021)
12-53939235-C-T		not specified	Uncertain significance (Dec 14, 2021)
12-53939241-C-T		not specified	Uncertain significance (Feb 09, 2022)
12-53939258-AC-A		Ectodermal dysplasia 9, hair/nail type	Pathogenic (Apr 01, 2013)
12-53939265-G-T		not specified	Uncertain significance (Feb 06, 2023)
12-53939273-T-C		not specified	Uncertain significance (Sep 20, 2023)
12-53939276-C-T		not specified	Uncertain significance (Jan 09, 2024)
12-53939292-A-G		not specified	Uncertain significance (Apr 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXC13	protein_coding	protein_coding	ENST00000243056	2	7794

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.420	0.573	120120	0	2	120122	0.00000832

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.550	142	162	0.878	0.00000774	2081
Missense in Polyphen		55	65.5	0.8397		908
Synonymous	0.737	67	75.1	0.892	0.00000375	689
Loss of Function	2.26	2	9.54	0.210	4.10e-7	118

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000183	0.0000183
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor which plays a role in hair follicle differentiation. Regulates FOXQ1 expression and that of other hair-specific genes (By similarity). {ECO:0000250}.
• Disease: DISEASE: Ectodermal dysplasia 9, hair/nail type (ECTD9) [MIM:614931]: 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. ECTD9 is characterized by hypotrichosis and nail dystrophy without non-ectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia). {ECO:0000269|PubMed:23063621, ECO:0000269|PubMed:28297138}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.121

Haploinsufficiency Scores

• pHI: 0.439
• hipred: Y
• hipred_score: 0.670
• ghis: 0.431

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hoxc13
• 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); craniofacial phenotype; vision/eye 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: hair follicle development;anatomical structure morphogenesis;anterior/posterior pattern specification;nail development;tongue morphogenesis;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;protein binding;sequence-specific DNA binding