HOXA11

homeobox A11, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 7:27181157-27185232

Previous symbols: [ "HOX1I", "HOX1" ]

Links

ENSG00000005073 ∙ NCBI:3207 ∙ OMIM:142958 ∙ HGNC:5101 ∙ Uniprot:P31270 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (Limited), mode of inheritance: AD
• radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (Supportive), mode of inheritance: AD
• radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (Limited), mode of inheritance: AD
• radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Radioulnar synostosis with amegakaryocytic thrombocytopenia 1	AD	Hematologic	Individuals can have symptomatic thrombocytopenia and bone marrow failure manifesting in the neonatal period, requiring early bone marrow/umbilical cord stem cell transplantation	Hematologic; Musculoskeletal	11101832; 11442476; 16765069; 20562651

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXA11 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXA11 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4		4
missense			32	4	1	37
nonsense						0
start loss						0
frameshift						0
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	32	9	4

Variants in HOXA11

This is a list of pathogenic ClinVar variants found in the HOXA11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-27182790-G-A		not specified	Benign/Likely benign (Aug 01, 2024)
7-27182857-A-C		Mesomelic dysplasia with urogenital abnormalities	Likely pathogenic (Jan 23, 2023)
7-27182865-GT-G		Radioulnar synostosis with amegakaryocytic thrombocytopenia 1	Pathogenic (Dec 01, 2000)
7-27182898-G-A		not specified	Benign/Likely benign (Jul 01, 2024)
7-27182919-T-A		not specified	Uncertain significance (Apr 11, 2024)
7-27182963-C-T		Inherited genitourinary tract anomalies	Likely pathogenic (Jul 07, 2020)
7-27183023-G-T		not specified	Uncertain significance (Mar 25, 2022)
7-27183024-G-T		HOXA11-related disorder	Likely benign (Mar 12, 2021)
7-27184152-C-T			Benign (Jun 19, 2021)
7-27184442-C-A		not specified	Uncertain significance (Jul 14, 2022)
7-27184466-C-G			Uncertain significance (Dec 17, 2022)
7-27184520-C-T			Uncertain significance (Apr 10, 2017)
7-27184536-C-A		HOXA11-related disorder	Likely benign (Nov 26, 2019)
7-27184541-C-G		not specified	Uncertain significance (Aug 30, 2022)
7-27184541-C-T		not specified	Uncertain significance (Mar 01, 2024)
7-27184550-C-A		not specified	Uncertain significance (May 08, 2023)
7-27184585-G-C		not specified	Uncertain significance (May 27, 2022)
7-27184588-G-T		not specified	Uncertain significance (Nov 08, 2022)
7-27184591-C-T		not specified	Uncertain significance (Apr 11, 2023)
7-27184599-AGCC-A		HOXA11-related disorder	Likely benign (Sep 12, 2019)
7-27184613-C-T		not specified	Uncertain significance (Jun 09, 2022)
7-27184626-C-A		HOXA11-related disorder	Likely benign (Jul 14, 2021)
7-27184633-G-T		not specified • HOXA11-related disorder	Likely benign (Sep 27, 2022)
7-27184636-G-T		HOXA11-related disorder	Uncertain significance (Aug 29, 2023)
7-27184637-G-A		not specified	Uncertain significance (May 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXA11	protein_coding	protein_coding	ENST00000006015	2	3714

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.943	0.0564	124889	0	1	124890	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.668	144	168	0.855	0.00000846	2012
Missense in Polyphen		41	69.611	0.58899		829
Synonymous	-2.06	96	73.5	1.31	0.00000368	648
Loss of Function	2.79	0	9.08	0.00	4.44e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000889	0.00000889
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Disease: DISEASE: Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (RUSAT1) [MIM:605432]: The syndrome consists of an unusual association of bone marrow failure and skeletal defects. Patients have the same skeletal defects, the proximal fusion of the radius and ulna, resulting in extremely limited pronation and supination of the forearm. Some patients have also symptomatic thrombocytopenia, with bruising and bleeding problems since birth, necessitating correction by bone marrow or umbilical- cord stem-cell transplantation. {ECO:0000269|PubMed:11101832}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.216
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.375
• hipred: Y
• hipred_score: 0.837
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hoxa11
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; reproductive system 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)

Gene ontology

• Biological process: skeletal system development;metanephros development;branching involved in ureteric bud morphogenesis;organ induction;regulation of transcription by RNA polymerase II;multicellular organism development;spermatogenesis;single fertilization;mesodermal cell fate specification;male gonad development;anatomical structure morphogenesis;anterior/posterior pattern specification;dorsal/ventral pattern formation;proximal/distal pattern formation;positive regulation of cell development;embryonic limb morphogenesis;positive regulation of chondrocyte differentiation;embryonic forelimb morphogenesis;embryonic digit morphogenesis;positive regulation of transcription, DNA-templated;developmental growth;uterus development;embryonic skeletal joint morphogenesis;cartilage development involved in endochondral bone morphogenesis
• Cellular component: nucleoplasm;transcription factor complex;protein-containing complex;protein-DNA complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding