HOXD1

protein-coding

homeobox D1, the group of HOXL subclass homeoboxes|MicroRNA protein coding host genes

Gene summary

This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. This nuclear protein functions as a sequence-specific transcription factor that is involved in differentiation and limb development. Mutations in this gene have been associated with severe developmental defects on the anterior-posterior (a-p) limb axis. [provided by RefSeq, Jul 2008]

Previous symbols:

HOX4
HOX4G

MANE transcript

NM_024501.3

Inheritance

—

ClinVar variants

U:48B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr2:176,188,668-176,190,907

External References & Databases

Ensembl (ENSG00000128645)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 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 HOXD1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024501.3. 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						0
missense			46 clinvar	1 clinvar		47
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	48	1	0	49

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024501.3	RefSeq	NP_078777.1	2	MANE Select
ENST00000331462.6	Ensembl	ENSP00000328598.4	2	MANE Select
ENST00000876788.1	Ensembl	ENSP00000546847.1	2	Standard
ENST00000876788.2	Ensembl	ENSP00000546847.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Activation of anterior HOX genes in hindbrain development during early embryogenesis

Biological Process

regulation of transcription by RNA polymerase II
sensory perception of pain
neuron differentiation
embryonic skeletal system development

Molecular Function

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

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331462
Coding exons: 2
Length: 2382
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0362	173	172	1.01	0.00000780	2047
Missense (PolyPhen)		50	48.21	1.0371		606
Synonymous	0.128	78	79.4	0.982	0.00000384	719
Loss of Function	1.16	5	8.70	0.575	3.88e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0018	0.00087	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00016	0.00016	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. Acts on the anterior body structures.;

Recessive Scores

pRec: 0.112

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.593

Gene Damage Prediction

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