HOXC5

protein-coding

homeobox C5, the group of HOXL subclass homeoboxes|MicroRNA protein coding host genes

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, HOXC5, is one of several homeobox HOXC genes located in a cluster on chromosome 12. Three genes, HOXC5, HOXC4 and HOXC6, share a 5' non-coding exon. Transcripts may include the shared exon spliced to the gene-specific exons, or they may include only the gene-specific exons. Two alternatively spliced variants have been described for HOXC5. The transcript variant which includes the shared exon apparently doesn't encode a protein. The protein-coding transcript variant contains gene-specific exons only. [provided by RefSeq, Jul 2008]

Previous symbols:

HOX3D
HOX3

MANE transcript

NM_018953.4

Inheritance

—

ClinVar variants

U:38B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr12:54,033,050-54,035,361

External References & Databases

Ensembl (ENSG00000172789)

Transcript & Mutation Effects

hg38 • Region Span ~2.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HOXC5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018953.4. 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					1 clinvar	1
missense			38 clinvar		1 clinvar	39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	38	0	2	40

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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_018953.4	RefSeq	NP_061826.1	2	MANE Select
ENST00000312492.3	Ensembl	ENSP00000309336.2	2	MANE Select
ENST00001142737.1	Ensembl	ENSP00000806046.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
anterior/posterior pattern specification
positive regulation of transcription by RNA polymerase II
embryonic skeletal system development

Molecular Function

RNA polymerase II distal enhancer sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription factor activity

Cellular Component

nucleus
nucleoplasm
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000312492
Coding exons: 2
Length: 2506
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.578	146	128	1.14	0.00000595	1437
Missense (PolyPhen)		48	37.475	1.2809		469
Synonymous	0.139	50	51.3	0.975	0.00000236	422
Loss of Function	0.422	7	8.31	0.842	3.58e-7	91

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000060	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00039	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.;

Intolerance Scores

LoFtool: 0.377
RVIS EVS: 0.08
RVIS percentile EVS: 59.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.760

Gene Damage Prediction

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