HOXB13

protein-coding

homeobox B13, the group of HOXL subclass homeoboxes

Gene summary

This gene encodes a transcription factor that belongs to the homeobox gene family. Genes of this family are highly conserved among vertebrates and essential for vertebrate embryonic development. This gene has been implicated to play a role in fetal skin development and cutaneous regeneration. In mice, a similar gene was shown to exhibit temporal and spatial colinearity in the main body axis of the embryo, but was not expressed in the secondary axes, which suggests functions in body patterning along the axis. This gene and other HOXB genes form a gene cluster at chromosome the 17q21-22 region. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006361.6

Inheritance

ClinVar variants

P:2U:1273B:384

Top phenotype

Prostate cancer, hereditary, 9

gnomAD constraint

pLI —, LoF o/e 1.07

Max pathogenic AF

—

Genomic locus

chr17:48,724,763-48,728,750

External References & Databases

Ensembl (ENSG00000159184)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

prostate cancer, hereditary, 9STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012597

Submitter: Labcorp Genetics (formerly Invitae)

prostate cancerDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008315

Submitter: Illumina

Clinical Genomic Database (CGD)

Prostate cancer, hereditary, 9AD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Individuals with certain variants in the gene may be at increased risk of prostate cancer, and ensuring appropriate surveillance may be beneficial

Refs: 22236224

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HOXB13 variants in ClinVar

13 Conditions Cataloged

not providedTotal: 1023

Hereditary cancer-predisposing syndromeTotal: 946

Prostate cancer, hereditary, 1Total: 627

Prostate cancer, hereditary, 9Total: 288

HOXB13-related disorderTotal: 54

not specifiedTotal: 20

Gastric cancerTotal: 6

Prostate cancerTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006361.6. 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			59 clinvar	309 clinvar	28 clinvar	396
missense		1 clinvar	893 clinvar	47 clinvar		941
nonsense	1 clinvar		46 clinvar			47
start loss			5 clinvar			5
frameshift			264 clinvar			264
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	1	1273	356	28	1659

Highest pathogenic variant AF is 0.0017336177

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_006361.6	RefSeq	NP_006352.2	2	MANE Select
ENST00000290295.8	Ensembl	ENSP00000290295.8	2	MANE Select
ENST00001143312.1	Ensembl	ENSP00000804766.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of Androgen receptor activity

Biological Process

negative regulation of transcription by RNA polymerase II
angiogenesis
epidermis development
response to wounding
response to testosterone

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
methyl-CpG binding
sequence-specific DNA binding

Cellular Component

nucleoplasm
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290295
Coding exons: 2
Length: 4416
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00415	166	166	1.00	0.00000840	1803
Missense (PolyPhen)		55	58.371	0.94224		699
Synonymous	-0.588	79	72.6	1.09	0.00000391	614
Loss of Function	-0.208	11	10.3	1.07	4.95e-7	113

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00013	0.00013	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. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000269|PubMed:28473536}.;
Disease: DISEASE: Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:22236224, ECO:0000269|PubMed:22714738, ECO:0000269|PubMed:23064873, ECO:0000269|PubMed:23292082, ECO:0000269|PubMed:25629170, ECO:0000269|PubMed:27424772}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.364
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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