HOXC13

protein-coding

homeobox C13, the group of HOXL subclass homeoboxes

Gene summary

This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. The product of this gene may play a role in the development of hair, nail, and filiform papilla. [provided by RefSeq, Jul 2008]

Previous symbols:

HOX3
HOX3G

MANE transcript

NM_017410.3

Inheritance

AR, AD

ClinVar variants

P:5U:74B:11

Top phenotype

Ectodermal dysplasia 9

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr12:53,938,831-53,946,544

External References & Databases

Ensembl (ENSG00000123364)

Transcript & Mutation Effects

hg38 • Region Span ~7.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ectodermal dysplasia 9, hair/nail typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013976

Submitter: PanelApp Australia

ectodermal dysplasia 9, hair/nail typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013976

Submitter: G2P

ectodermal dysplasia 9, hair/nail typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013976

Submitter: Labcorp Genetics (formerly Invitae)

pure hair and nail ectodermal dysplasiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019071

Submitter: Orphanet

ectodermal dysplasia 9, hair/nail typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013976

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Ectodermal dysplasia 9AR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 23063621

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HOXC13 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 21

Ectodermal dysplasia 9, hair/nail typeTotal: 9

HOXC13-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017410.3. 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				8 clinvar		8
missense			71 clinvar	3 clinvar		74
nonsense	1 clinvar					1
start loss						0
frameshift	3 clinvar	1 clinvar	3 clinvar			7
splice donor/acceptor (+/-2bp)						0
Total	4	1	74	11	0	90

Highest pathogenic variant AF is 0.00009671852

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_017410.3	RefSeq	NP_059106.2	2	MANE Select
ENST00000243056.5	Ensembl	ENSP00000243056.3	2	MANE Select
ENST00001142801.1	Ensembl	ENSP00000802304.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

hair follicle development
anatomical structure morphogenesis
anterior/posterior pattern specification
nail development
tongue morphogenesis

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000243056
Coding exons: 2
Length: 7794
Individuals with no LoFs: 120120
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 120122
p: 0.00000832

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.550	142	162	0.878	0.00000774	2081
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

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