HOXD13 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- HOXD13 (HGNC:5136) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- homeobox D13
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- HOX4I, SPD
- Alias symbols
- No aliases found
- %HI
- 2.62(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 0.96(Read more about gnomAD LOEUF score)
- Cytoband
- 2q31.1
- Genomic Coordinates
-
GRCh37/hg19: chr2:176957449-176960672 NCBI Ensembl UCSC GRCh38/hg38: chr2:176087487-176095944 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000523.4 ENST00000392539.4 (Read more about MANE Select)
- Function
- Sequence-specific transcription factor that binds gene promoters and activates their transcription (PubMed:24789103). Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis (By similarity). {ECO:0000250|UniProtKB:P24344, ECO:0000269|PubMed:24789103}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-23568
ClinGen Curation ID:
CCID:007292
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
09/23/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- synpolydactyly type 1 Monarch
HI Evidence:
-
PUBMED:
31611522
In 2019, Guo et al. used trio whole-exome sequencing (trio-WES) on an individual with synopolydactyly (SPD) and their parents. Analysis identified a nonsense variant (p.Gln287Ter) in HOXD13 in the proband and the affected father. Per the authors, “Mutation Taster, Human Splicing Finder and EX-SKIP predicted that the heterozygous mutation (c.859 C>T) would result in haploinsufficiency of HOXD13 protein through nonsense-mediated mRNA decay (NMD) and splicing abnormality, which might disrupt the integrity and reduce the expression level of the HOXD13 protein (loss-of-function).” This variant was absent in the unaffected mother and grandmother.
-
PUBMED:
22233338
In 2012, Jamsheer et al. used PCR, direct sequencing, and multiplex ligation-dependent analysis (MLPA) on a family with brachydactyly (BDE) to identify potential variants in HOXD13. The authors identified a nonsense variant in the proband and her affected father (p.R274X).
-
PUBMED:
9758628
In 1998, Goodman et al. used PCR to identify potential variants in HOXD13 in 2 families with digital abnormalities. In family 1, a 14-base pair deletion resulting in a frameshift variant and truncated protein product was identified in the proband and 3 other family members. However, only the proband displayed digital abnormalities. In family 2, a different frameshift variant resulting in a premature stop codon was identified in the proband, 4 affected family members, and 2 unaffected family members.
HI Evidence Comments:
There are many variations in disease phenotype with HOXD13 including Brachydactyly, Syndactyly, Synpolydactyly with foot anomalies, and VACTERL association.
Additional cases:
PMID: 21814222
In 2011, Kurban et al. used PCR and direct sequencing on consanguineous family members with variable presentations of synopolydactyly (SPD). Analysis identified the nonsense variant p.Q248X in HOXD13. 6 individuals carry the variant in a heterozygous manner and are unaffected, 16 individuals are affected. Of these affected individuals, 10 are homozygous for the variant and 6 are heterozygous for the variant. The authors note that individuals carrying the variant in the homozygous state were more severely affected than those with the heterozygous presentation who either displayed mild SPD or were unaffected.
Per the authors, “because of the high rate of consanguinity, the inheritance pattern was most likely autosomal recessive, while there was also the possibility of autosomal dominant inheritance with incomplete penetrance. We initially performed parametric linkage analysis, which was non-revealing. We then performed nonparametric linkage analysis and identified linkage to a region on chromosome 2 containing the HOXD13 gene, under an autosomal dominant inheritance model.”
PMID: 27254532
In 2017, Wang et al. used whole exome sequencing (WES) on a family with synopolydactyly (SPD). Analysis identified a novel nonsense variant (p.R186X) resulting in protein truncation in HOXD13 in the proband. The variant was identified in 4 affected relatives and absent in 3 unaffected relatives who were given testing.
PMID: 12900906
In 2003, Kan et al. used PCR on a family with limb malformations. Analysis identified a variant affecting splicing in HOXD13 in the proband and 2 other affected family members (758-2delA).
PMID: 24055421
In 2013, Shi et al. used PCR and direct sequencing on a family with type II synopolydactyly (SPD1). The authors identified a splice site variant in the proband and their 4 affected family members.
PMID: 17236141
In 2007, Zhao et al. used two-point linkage analysis and mutation identification on a family with limb abnormalities. The authors identified a 21-bp deletion in HOXD13 in 15 individuals of the family.
PMID: 19006232
In 2008, Garcia-Barcelo et al. used PCR on one patient with VACTERL and identified a de novo 21-bp deletion in HOXD13.
PMID: 32789964
In 2020, Zhang et al. used PCR on a family with brachydactyly type A (BDA). A frameshift deletion in HOXD13 was shown in 4 of the affected individuals of the family.
PMID: 28794915
In 2017, Radhakrishnan et al. used Sanger sequencing on a mother and fetus with synpolydactlyly and identified a deletion in HOXD13 in both individuals.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000002.11)
(NC_000002.12)