HOXD13
homeobox D13, the group of HOXL subclass homeoboxes
Basic information
Region (hg38): 2:176092721-176095944
Previous symbols: [ "HOX4I", "SPD" ]
Links
Phenotypes
GenCC
Source:
- brachydactyly-syndactyly syndrome (Definitive), mode of inheritance: AD
- brachydactyly-syndactyly syndrome (Strong), mode of inheritance: AD
- brachydactyly type E (Supportive), mode of inheritance: AD
- syndactyly type 5 (Supportive), mode of inheritance: AD
- brachydactyly-syndactyly syndrome (Supportive), mode of inheritance: AD
- synpolydactyly type 1 (Supportive), mode of inheritance: AD
- synpolydactyly type 1 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Brachydactyly-syndactyly syndrome; Brachydactyly, type D; Brachydactyly, type E1; Syndactyly, type V; Synopolydactyly, type I, Synopolydactyly, type II; Synopolydactyly with clefting, autosomal recessive | AD/AR | Renal | 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 | Craniofacial; Musculoskeletal | 7666393; 8817328; 8614804; 8933344; 9758628; 11778160; 12116248; 12649808; 12900906; 16222680; 17236141; 19006232; 18177473; 19060004; 20974300; 21814222; 22233338; 22373878; 22374128; 22406499; 22473151 |
| The condition has also been implicated in VACTERL association (AD), but the pathogenesis is unclear |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (90 variants)
- Inborn_genetic_diseases (42 variants)
- Synpolydactyly_type_1 (26 variants)
- HOXD13-related_disorder (17 variants)
- Brachydactyly_type_D (12 variants)
- Brachydactyly-syndactyly_syndrome (12 variants)
- Syndactyly_type_5 (11 variants)
- Brachydactyly_type_E1 (11 variants)
- not_specified (5 variants)
- Brachydactyly_type_E (2 variants)
- Brachydactyly-syndactyly-oligodactyly_syndrome (1 variants)
- Male_infertility (1 variants)
- Penile_hypospadias (1 variants)
- Intellectual_disability (1 variants)
- Oligospermia (1 variants)
- Mesoaxial_hand_polydactyly (1 variants)
- VATER_association (1 variants)
- Polydactyly (1 variants)
- Skeletal_dysplasia (1 variants)
- Syndactyly (1 variants)
- Synpolydactyly (1 variants)
- Abnormal_finger_morphology (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXD13 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000523.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | |||||
| missense | 75 | 91 | ||||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 10 | 11 | ||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 21 | 6 | 77 | 13 | 3 |
Highest pathogenic variant AF is 0.0000553244
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HOXD13 | protein_coding | protein_coding | ENST00000392539 | 2 | 3048 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00861 | 0.940 | 125717 | 0 | 30 | 125747 | 0.000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0420 | 159 | 161 | 0.991 | 0.00000751 | 2148 |
| Missense in Polyphen | 32 | 42.236 | 0.75765 | 521 | ||
| Synonymous | -0.961 | 80 | 69.8 | 1.15 | 0.00000354 | 738 |
| Loss of Function | 1.69 | 5 | 11.0 | 0.453 | 4.87e-7 | 124 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000714 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.000697 | 0.000693 |
| European (Non-Finnish) | 0.0000914 | 0.0000791 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000335 | 0.000326 |
dbNSFP
Source:
- Function
- 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}.;
- Disease
- DISEASE: Synpolydactyly 1 (SPD1) [MIM:186000]: Limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. {ECO:0000269|PubMed:12414828, ECO:0000269|PubMed:16222680, ECO:0000269|PubMed:24789103, ECO:0000269|PubMed:26581570, ECO:0000269|PubMed:8817328}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly D (BDD) [MIM:113200]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type D is characterized by short and broad terminal phalanges of the thumbs and big toes. {ECO:0000269|PubMed:12649808}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Syndactyly 5 (SDTY5) [MIM:186300]: A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. The characteristic finding in SDTY5 is the presence of an associated metacarpal and metatarsal fusion. The metacarpals and metatarsals most commonly fused are the 4th and 5th or the 3rd and 4th. Soft tissue syndactyly usually affects the 3rd and 4th fingers and the 2nd and 3rd toes. {ECO:0000269|PubMed:17236141}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly-syndactyly syndrome (BDSD) [MIM:610713]: A disease characterized by generalized shortening of the hands and feet, broad and short distal phalanges of the thumbs, and cutaneous syndactyly of toes 2 and 3. The limb phenotypes observed in this syndrome overlap those of brachydactyly types A4, D, E and syndactyly type 1. {ECO:0000269|PubMed:17236141}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly E1 (BDE1) [MIM:113300]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. Brachydactyly type E1 is characterized by shortening limited to fourth metacarpals and/or metatarsals. {ECO:0000269|PubMed:12649808, ECO:0000269|PubMed:24789103}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: VACTERL association (VACTERL) [MIM:192350]: VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. {ECO:0000269|PubMed:19006232}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Brachydactyly-syndactyly-oligodactyly syndrome (BDSDO) [MIM:610713]: A syndrome characterized by a complex brachydactyly- syndactyly-oligodactyly phenotype. Limb anomalies include reduced number of digits that are severely shortened, camptodactyly, syndactyly, absence of terminal phalanges of the thumbs, and absence of nails of the thumbs and toes. {ECO:0000269|PubMed:23995701}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.409
Intolerance Scores
- loftool
- 0.163
- rvis_EVS
- -0.1
- rvis_percentile_EVS
- 46.49
Haploinsufficiency Scores
- pHI
- 0.832
- hipred
- Y
- hipred_score
- 0.559
- ghis
- 0.444
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.880
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hoxd13
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype;
Gene ontology
- Biological process
- skeletal system development;regulation of transcription, DNA-templated;transcription by RNA polymerase II;multicellular organism development;anterior/posterior pattern specification;male genitalia development;response to testosterone;regulation of cell population proliferation;embryonic digit morphogenesis;positive regulation of transcription by RNA polymerase II;embryonic hindgut morphogenesis;prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis;morphogenesis of an epithelial fold;branch elongation of an epithelium;regulation of branching involved in prostate gland morphogenesis
- Cellular component
- nucleus
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity