HOXA11

Summary

HOXA11 (homeobox A11, HGNC:5101) is a protein-coding gene on chromosome 7p15.2, encoding Homeobox protein Hox-A11 (P31270). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radio-ulnar synostosis with amegakaryocytic thrombocytopenia.

Source: NCBI Gene 3207 — RefSeq curated summary.

At a glance

• Gene–disease (curated): radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 35
• Clinical variants (ClinVar): 84 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 19
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_005523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5101
Approved symbol	HOXA11
Name	homeobox A11
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000005073
Ensembl biotype	protein_coding
OMIM	142958
Entrez	3207

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000006015, ENST00000517402

RefSeq mRNA: 1 — MANE Select: NM_005523 NM_005523

CCDS: CCDS5411

Canonical transcript exons

ENST00000006015 — 2 exons

Exon	Start	End
ENSE00001147062	27184436	27185232
ENSE00002099557	27181157	27183028

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 94.65.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6805 / max 235.4870, expressed in 600 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83330	2.6576	531
83329	1.7754	420
83331	0.2475	169

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	94.65	gold quality
myometrium	UBERON:0001296	92.17	gold quality
endocervix	UBERON:0000458	90.91	gold quality
stromal cell of endometrium	CL:0002255	90.66	gold quality
uterus	UBERON:0000995	89.73	gold quality
endometrium	UBERON:0001295	88.50	gold quality
ectocervix	UBERON:0012249	85.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.06	gold quality
uterine cervix	UBERON:0000002	82.57	gold quality
sigmoid colon	UBERON:0001159	80.61	gold quality
tibial artery	UBERON:0007610	79.84	gold quality
popliteal artery	UBERON:0002250	79.78	gold quality
type B pancreatic cell	CL:0000169	79.49	gold quality
transverse colon	UBERON:0001157	79.42	gold quality
olfactory bulb	UBERON:0002264	79.35	gold quality
prostate gland	UBERON:0002367	79.13	gold quality
urinary bladder	UBERON:0001255	78.24	gold quality
metanephros cortex	UBERON:0010533	77.69	gold quality
cervix epithelium	UBERON:0004801	77.62	silver quality
mucosa of urinary bladder	UBERON:0001259	77.60	gold quality
gastrocnemius	UBERON:0001388	77.45	gold quality
triceps brachii	UBERON:0001509	77.43	gold quality
cervix squamous epithelium	UBERON:0006922	77.12	gold quality
colon	UBERON:0001155	77.05	gold quality
muscle of leg	UBERON:0001383	76.87	gold quality
large intestine	UBERON:0000059	76.75	gold quality
cauda epididymis	UBERON:0004360	76.38	gold quality
mucosa of transverse colon	UBERON:0004991	75.84	gold quality
muscle organ	UBERON:0001630	75.70	gold quality
gluteal muscle	UBERON:0002000	75.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.53
E-MTAB-7249	no	64.67

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
ASXL3
CAT
COL3A1	Unknown
EGFR
HOXA10	Repression
HOXA11
MMP2	Repression
MYOD1	Repression
PRL	Activation
TP53	Repression

JASPAR motifs

Motif	Name	Family
MA0911.1	Hoxa11	HOX
MA0911.2	Hoxa11	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): HOXA11, HOXA13, KDM6A, KMT2A

miRNA regulators (miRDB)

93 targeting HOXA11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809

Literature-anchored findings (GeneRIF, showing 40)

• NUP98 primer and a degenerate primer corresponding to the third helix of the homeodomain of HOXA demonstrated that NUP98 was fused in-frame to HOXA11 in the patient with CML ( chronic myelogenous leukemia) (PMID:11830496)
• expressed in the developing kidney (PMID:12060755)
• HOXA gene expression is up-regulated at the ectopic implantation site in the fallopian tube and it may play a role in ectopic pregnancies. (PMID:15167850)
• study reveals a novel expression pattern for homeo box A11(HOXA11) gene in human endometrium (PMID:15467538)
• The HOXA11 gene cluster is in T-cell malignancies resulting in deregulated HOXA gene expression and is in keeping with a previous report suggesting HOXA deregulation in MLL-rearranged T cell lymphoblastic leukemia. (PMID:15674412)
• HOXA10 and HOXA11 expression increases during the menstrual cycle, increasing drastically in the midluteal phase, at the time of implantation. (PMID:15731295)
• HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. (PMID:18274672)
• Our findings do not support the hypothesis that mutations in the HOXA11 coding regions are involved in the pathogenesis of human non-syndromal congenital renal parenchymal malformations. (PMID:19255789)
• Expression of HOXA11 represses the expression of p53 in uterosacral ligaments. (PMID:19372592)
• Methylation of HOXA11 gene is associated with high-grade squamous intraepithelial lesions in cervical cancer (PMID:19609949)
• HoxA-11 is required for prolactin expression in decidualized embryonic stem cells and turns into an activator when combined with FOXO1A; HOXA-10 is unable to upregulate PRL expression when co-expressed with FOXO1A (PMID:19727442)
• No subject with female genital tract anomalies showed a plausible causative mutation in HOX A10 or HOX A11. (PMID:20457539)
• Our results suggest that altered HOXA11 gene expression in the endometrium during a menstrual cycle may be a common phenomenon among patients with endometriosis and may cause infertility in this group of patients (PMID:20695189)
• The result suggest that HOXA-11 gene expression in the endometrium during the implantation window may not be altered in patients with idiopathic infertility. (PMID:21526497)
• Endometrial HOXA11 and LIF mRNA expression levels (normalized to beta-actin expression) were significantly decreased in endometrium of infertile patients with endometriosis compared with healthy fertile controls (PMID:21987111)
• reduced HOXA11 expression may contribute to endometriosis-associated infertility (PMID:22233680)
• Data show that up-regulation of the HOXA7, HOXA9, HOXA11, and PBX3 resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable cytogenetically abnormal AML (CA-AML). (PMID:22251480)
• Promoter methylation of HOXA11 is associated with glioblastoma. (PMID:23624749)
• Lower expression of HOXA11 is associated with endometriosis-associated infertility. (PMID:23979130)
• Study suggests that HOXA11 hypermethylation may contribute to the progression of NSCLC by promoting cell proliferation or migration. (PMID:24259349)
• Low HOXA11 expression is associated with hepatocellular carcinoma. (PMID:24306662)
• Mutations in the coding region of HOXA11 are not common in Chinese women with Mullerian duct anomalies. (PMID:24745830)
• Epigenetic silencing of HOXA11 promotes gastric cancer proliferation, migration and invasion through activation of Wnt signaling. (PMID:25590359)
• The overexpression of miR-30d or 181a suppressed HOXA11 mRNA. (PMID:25630974)
• Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-11 mRNA expression. (PMID:26056923)
• Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. (PMID:26552702)
• The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. (PMID:27456940)
• Hypermethylation of HOXA11 is an independent prognostic biomarker in breast cancer. Suggest HOXA11 as a potential tumor suppressor. (PMID:28038461)
• These results suggest that mutations in the coding sequence of HOXA11 might not be a common cause of cryptorchidism, while common polymorphisms in the HOXA11 gene might contribute to the risk of developing unilateral cryptorchidism. (PMID:28261830)
• We conclude that the expression patterns of HoxA10, HoxA11, and HoxA13 and their actions in regulating CAP genes in the uterus create regionalized myometrium phenotypes in women that may be important to control regionalized myometrium contractility for maintaining pregnancy. (PMID:28372536)
• Results show that aberrant hypermethylation and the methylation-induced down-regulation of HOXA11 may promote lung adenocarcinoma progression. (PMID:28380439)
• our study demonstrated that HOXA11 function as a tumor suppressor in renal cell carcinoma (PMID:28423531)
• HOXA11 silencing suppressed osteosarcoma cell proliferation, invasion and induced cell arrest. (PMID:28558357)
• High expression of lncRNA HOXA11-AS promotes breast cancer invasion and metastasis by affecting EMT. (PMID:28701685)
• demonstrated that HOXA11-antisense(AS) functioned as a molecular sponge for miR-124, and overexpression of miR-124 attenuated the proliferation and invasion-promoting effect of HOXA11-AS (PMID:28749709)
• Bioinformatics prediction forecast that miR-140-5p directly targeted HOXA11-antisense RNA at 3’-UTR, which was confirmed by luciferase reporter assay (PMID:28832185)
• HOXA11-AS functions as a competing endogenous RNA. (PMID:29034803)
• we uncovered a novel potential regulatory mechanism between HOTTIP and one of its physical HOXA clusters, HOXA11. Hence, HOTTIP may mediate, at least partly, HOXA11 expression involved in cell growth, migration, and apoptosis of breast cancer MCF-7 cells. (PMID:29415429)
• HOXA11 high expression might lead to the occurrence and development of lung squamous cancer. (PMID:29914539)
• HOXA11-AS regulates diabetic arteriosclerosis-related inflammation via PI3K/AKT pathway (PMID:30402857)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxa11b	ENSDARG00000007009
danio_rerio	hoxa11a	ENSDARG00000104162
mus_musculus	Hoxa11	ENSMUSG00000038210
rattus_norvegicus	Hoxa11	ENSRNOG00000059870

Paralogs (42): HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), HOXD13 (ENSG00000128714), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-A11 — P31270 (reviewed: P31270)

Alternative names: Homeobox protein Hox-1I

All UniProt accessions (2): P31270, H0YIA6

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Nucleus.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_005514* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR021918	DUF3528	Domain

Pfam: PF00046, PF12045

UniProt features (5 total): compositionally biased region 2, chain 1, DNA-binding region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31270-F1	62.09	0.21

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9830674	Formation of the ureteric bud

MSigDB gene sets: 380 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_SINGLE_FERTILIZATION, RRAGTTGT_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, BROWNE_HCMV_INFECTION_6HR_DN, HNF3ALPHA_Q6, GOBP_METANEPHROS_DEVELOPMENT, GOBP_CARTILAGE_DEVELOPMENT, MORF_MSH3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (34): skeletal system development (GO:0001501), metanephros development (GO:0001656), branching involved in ureteric bud morphogenesis (GO:0001658), organ induction (GO:0001759), chondrocyte development (GO:0002063), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), single fertilization (GO:0007338), mesodermal cell fate specification (GO:0007501), male gonad development (GO:0008584), anatomical structure morphogenesis (GO:0009653), anterior/posterior pattern specification (GO:0009952), dorsal/ventral pattern formation (GO:0009953), proximal/distal pattern formation (GO:0009954), positive regulation of cell development (GO:0010720), embryonic limb morphogenesis (GO:0030326), prostate gland development (GO:0030850), positive regulation of chondrocyte differentiation (GO:0032332), response to testosterone (GO:0033574), embryonic forelimb morphogenesis (GO:0035115), embryonic digit morphogenesis (GO:0042733), response to estrogen (GO:0043627), positive regulation of DNA-templated transcription (GO:0045893), developmental growth (GO:0048589), uterus development (GO:0060065), embryonic skeletal joint morphogenesis (GO:0060272), cartilage development involved in endochondral bone morphogenesis (GO:0060351), positive regulation of chondrocyte development (GO:1902761), chondrocyte differentiation (GO:0002062), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), regulation of chondrocyte differentiation (GO:0032330), cell development (GO:0048468), bone development (GO:0060348)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regionalization	3
chondrocyte differentiation	2
cell development	2
positive regulation of cell differentiation	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
protein-containing complex	2
system development	1
kidney development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
regulation of animal organ formation	1
specification of animal organ identity	1
developmental induction	1
positive regulation of animal organ morphogenesis	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
developmental process involved in reproduction	1
male gamete generation	1
fertilization	1
cell fate specification	1
mesodermal cell fate commitment	1
gonad development	1
development of primary male sexual characteristics	1
developmental process	1
anatomical structure development	1
regulation of cell development	1
limb morphogenesis	1
embryonic appendage morphogenesis	1
urogenital system development	1
reproductive structure development	1
gland development	1
regulation of chondrocyte differentiation	1
positive regulation of cartilage development	1
response to lipid	1
response to ketone	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXA11	FOXO1	Q12778	797
HOXA11	PAX2	Q02962	757
HOXA11	EYA1	Q99502	662
HOXA11	EMX2	Q04743	628
HOXA11	PBX1	P40424	599
HOXA11	COL3A1	P02461	584
HOXA11	CDC6	Q99741	523
HOXA11	MMP2	P08253	508
HOXA11	NFE2L3	Q9Y4A8	507
HOXA11	SIX2	Q9NPC8	506
HOXA11	PRSS58	Q8IYP2	492
HOXA11	TAL1	P17542	485
HOXA11	MEIS1	O00470	472
HOXA11	ZIC2	O95409	469
HOXA11	GFI1	Q99684	467

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PGBD3	HOXA11	psi-mi:“MI:0915”(physical association)	0.370
PARP1	KPNA3	psi-mi:“MI:0914”(association)	0.350
PICALM	RPN1	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): HOXA11 (Affinity Capture-MS), HOXA11 (Affinity Capture-MS), HOXA11 (Affinity Capture-MS), HOXA11 (Affinity Capture-MS), HOXA11 (Affinity Capture-MS), HOXA11 (Affinity Capture-MS), HOXA11 (Affinity Capture-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS), HOXA11 (Proximity Label-MS)

ESM2 similar proteins: A1YEY5, A1YFA5, A1YFI3, A1YG57, A1YGK7, A2T733, A2T7F3, A2T7P4, A6NJ46, O43248, P02830, P02832, P04476, P09019, P09021, P09023, P09024, P09629, P09632, P15861, P17481, P17509, P18864, P23812, P24344, P31259, P31267, P31268, P31270, P31311, P35453, P53545, P56915, P70217, P97334, Q02591, Q1KKX1, Q1KKY1, Q1KKY3, Q1KKZ5

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, B5DFK3, O42502, O42503, O42506, O43248, P09013, P09014, P09023, P09025, P09067, P09079, P09087, P09631, P09632, P09633, P10179, P14838, P15861, P17481, P17482, P17509, P18863, P18866, P20615, P23459, P23813, P24340, P24341, P24342, P28356, P28357, P28358, P28359, P31257

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HOXA11	“down-regulates quantity by repression”	HOXA10	“transcriptional regulation”
KDM6A	“up-regulates quantity by expression”	HOXA11	“transcriptional regulation”
HOXA11	“up-regulates quantity by expression”	PRL	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

84 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	60
Likely benign	9
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
14897	NM_005523.6(HOXA11):c.872del (p.Asn291fs)	Pathogenic
2203766	NM_005523.6(HOXA11):c.881T>G (p.Met294Arg)	Likely pathogenic
2664263	NM_005523.6(HOXA11):c.775G>A (p.Glu259Lys)	Likely pathogenic

SpliceAI

405 predictions. Top by Δscore:

Variant	Effect	Δscore
7:27183024:GCCAC:G	acceptor_gain	1.0000
7:27183025:CCAC:C	acceptor_gain	1.0000
7:27183025:CCACC:C	acceptor_gain	1.0000
7:27183026:CAC:C	acceptor_gain	1.0000
7:27183026:CACC:C	acceptor_gain	1.0000
7:27183027:AC:A	acceptor_gain	1.0000
7:27183027:ACCT:A	acceptor_loss	1.0000
7:27183028:CC:C	acceptor_gain	1.0000
7:27183029:C:CC	acceptor_gain	1.0000
7:27183030:T:A	acceptor_loss	1.0000
7:27184434:A:AC	donor_gain	1.0000
7:27184435:C:CC	donor_gain	1.0000
7:27183031:G:C	acceptor_gain	0.9900
7:27183031:G:GC	acceptor_gain	0.9900
7:27184398:C:A	donor_gain	0.9900
7:27184431:CGTA:C	donor_gain	0.9900
7:27184432:GTA:G	donor_loss	0.9900
7:27184433:TA:T	donor_loss	0.9900
7:27184434:ACTG:A	donor_loss	0.9900
7:27184435:C:CA	donor_loss	0.9900
7:27184435:CT:C	donor_gain	0.9800
7:27184435:CTG:C	donor_gain	0.9800
7:27184435:CTGG:C	donor_gain	0.9800
7:27184435:CTGGA:C	donor_gain	0.9800
7:27184397:C:CA	donor_gain	0.9700
7:27183029:C:T	acceptor_gain	0.9600
7:27183501:A:C	donor_gain	0.9600
7:27184430:ACGT:A	donor_loss	0.9600
7:27183469:T:A	donor_gain	0.9500
7:27183495:T:TA	donor_gain	0.9500

AlphaMissense

2032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:27182836:C:A	R301I	1.000
7:27182844:T:A	K298N	1.000
7:27182844:T:G	K298N	1.000
7:27182845:T:A	K298I	1.000
7:27182846:T:C	K298E	1.000
7:27182847:T:A	K297N	1.000
7:27182847:T:G	K297N	1.000
7:27182848:T:A	K297I	1.000
7:27182849:T:C	K297E	1.000
7:27182849:T:G	K297Q	1.000
7:27182852:C:T	E296K	1.000
7:27182853:C:A	K295N	1.000
7:27182853:C:G	K295N	1.000
7:27182854:T:A	K295M	1.000
7:27182854:T:G	K295T	1.000
7:27182855:T:C	K295E	1.000
7:27182855:T:G	K295Q	1.000
7:27182856:C:A	M294I	1.000
7:27182856:C:G	M294I	1.000
7:27182856:C:T	M294I	1.000
7:27182857:A:C	M294R	1.000
7:27182857:A:G	M294T	1.000
7:27182857:A:T	M294K	1.000
7:27182859:T:A	R293S	1.000
7:27182859:T:G	R293S	1.000
7:27182860:C:A	R293I	1.000
7:27182860:C:G	R293T	1.000
7:27182861:T:C	R293G	1.000
7:27182862:C:A	R292S	1.000
7:27182862:C:G	R292S	1.000

dbSNP variants (sampled 300 via entrez): RS1001749900 (7:27183536 A>C), RS1001802119 (7:27183165 G>C), RS1002295658 (7:27186580 T>C), RS1002424431 (7:27186847 T>G), RS1003026208 (7:27183516 G>A), RS1003386 (7:27186509 G>C), RS1003933308 (7:27185296 T>C), RS1004043378 (7:27185532 T>A,C), RS1004731097 (7:27185266 T>A,G), RS1005173569 (7:27182026 G>A), RS1005659052 (7:27182193 G>T), RS1006379795 (7:27180779 C>T), RS1006516372 (7:27184125 T>A), RS1006624094 (7:27180975 C>A,G), RS1006682271 (7:27186604 G>A)

Disease associations

OMIM: gene MIM:142958 | disease phenotypes: MIM:605432

GenCC curated gene-disease

Disease	Classification	Inheritance
radioulnar synostosis with amegakaryocytic thrombocytopenia 1	Strong	Autosomal dominant
radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
radioulnar synostosis with amegakaryocytic thrombocytopenia 1	Limited	AD

Mondo (3): radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (MONDO:0024558), thrombocytopenia (MONDO:0002049), radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (MONDO:0011555)

Orphanet (1): Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (Orphanet:71289)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000967	Petechiae
HP:0000979	Purpura
HP:0001159	Syndactyly
HP:0001385	Hip dysplasia
HP:0001905	Congenital thrombocytopenia
HP:0001915	Aplastic anemia
HP:0002827	Hip dislocation
HP:0002974	Radioulnar synostosis
HP:0002986	Radial bowing
HP:0003031	Ulnar bowing
HP:0003182	Shallow acetabular fossae
HP:0004209	Clinodactyly of the 5th finger
HP:0004859	Amegakaryocytic thrombocytopenia
HP:0005037	Proximal radio-ulnar synostosis
HP:0005548	Megakaryocytopenia
HP:0006101	Finger syndactyly
HP:0006394	Limited pronation/supination of forearm

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST002782_172	Waist-to-hip ratio adjusted for body mass index	8.000000e-06
GCST002782_173	Waist-to-hip ratio adjusted for body mass index	2.000000e-06
GCST002782_174	Waist-to-hip ratio adjusted for body mass index	4.000000e-10
GCST002782_175	Waist-to-hip ratio adjusted for body mass index	1.000000e-06
GCST002782_176	Waist-to-hip ratio adjusted for body mass index	7.000000e-06
GCST002782_184	Waist-to-hip ratio adjusted for body mass index	3.000000e-10
GCST004063_1	Waist circumference adjusted for body mass index	8.000000e-11
GCST004063_16	Waist circumference adjusted for body mass index	2.000000e-07
GCST004063_45	Waist circumference adjusted for body mass index	2.000000e-06
GCST004064_35	Waist-hip ratio	5.000000e-08
GCST004500_10	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004500_133	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	9.000000e-08
GCST004501_89	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	1.000000e-07
GCST004504_63	Waist circumference adjusted for BMI in non-smokers	9.000000e-07
GCST004505_42	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004505_61	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	8.000000e-09
GCST004562_32	Waist circumference adjusted for body mass index	2.000000e-08
GCST004563_252	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004564_207	Waist circumference adjusted for BMI in active individuals	3.000000e-07
GCST004567_23	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	5.000000e-08
GCST004567_84	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	5.000000e-08
GCST004576_135	Waist-to-hip ratio adjusted for body mass index	1.000000e-06
GCST004576_19	Waist-to-hip ratio adjusted for body mass index	1.000000e-08
GCST004576_20	Waist-to-hip ratio adjusted for body mass index	6.000000e-09
GCST004578_125	Waist-to-hip ratio adjusted for BMI in active individuals	4.000000e-07
GCST004578_36	Waist-to-hip ratio adjusted for BMI in active individuals	4.000000e-07
GCST004578_52	Waist-to-hip ratio adjusted for BMI in active individuals	6.000000e-06
GCST004578_98	Waist-to-hip ratio adjusted for BMI in active individuals	6.000000e-06
GCST006288_144	Heel bone mineral density	5.000000e-07
GCST006288_589	Heel bone mineral density	2.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C565328	Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases methylation	2
Arsenic	increases methylation, decreases expression, increases abundance	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Bortezomib	decreases expression	1
Decitabine	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Vehicle Emissions	affects methylation, increases abundance	1
Benzo(a)pyrene	decreases expression, increases methylation	1
Methotrexate	decreases expression	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Progesterone	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Vitamin E	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Medroxyprogesterone Acetate	increases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

Clinical trials (associated diseases)

240 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT