BHLHA9

Summary

BHLHA9 (basic helix-loop-helix family member a9, HGNC:35126) is a protein-coding gene on chromosome 17p13.3, encoding Class A basic helix-loop-helix protein 9 (Q7RTU4). Transcription factor, which play a role in limb development.

This gene is a member of the basic helix-loop-helix family. The encoded protein is a transcription factor involved in limb development. Mutations in this gene have been associated with mesoaxial synostotic syndactyly Malik-Percin type (MSSD). Copy number variation of a locus containing this gene has been linked to a form of split-hand/foot malformation with long bone deficiency (SHFLD3).

Source: NCBI Gene 727857 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mesoaxial synostotic syndactyly with phalangeal reduction (Definitive, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 116 total — 12 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 46
• MANE Select transcript: NM_001164405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35126
Approved symbol	BHLHA9
Name	basic helix-loop-helix family member a9
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	BHLHF42
Ensembl gene	ENSG00000205899
Ensembl biotype	protein_coding
OMIM	615416
Entrez	727857

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391429

RefSeq mRNA: 1 — MANE Select: NM_001164405 NM_001164405

CCDS: CCDS45560

Canonical transcript exons

ENST00000391429 — 1 exons

Exon	Start	End
ENSE00001509211	1270444	1271815

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 91.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0060 / max 4.2035, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208020	0.0060	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.42	gold quality
prefrontal cortex	UBERON:0000451	58.23	gold quality
frontal cortex	UBERON:0001870	57.68	gold quality
right frontal lobe	UBERON:0002810	56.55	gold quality
primary visual cortex	UBERON:0002436	56.39	gold quality
cerebral cortex	UBERON:0000956	55.02	gold quality
superior frontal gyrus	UBERON:0002661	54.95	gold quality
anterior cingulate cortex	UBERON:0009835	52.90	gold quality
hypothalamus	UBERON:0001898	50.34	gold quality
temporal lobe	UBERON:0001871	49.01	gold quality
amygdala	UBERON:0001876	48.75	gold quality
colonic epithelium	UBERON:0000397	45.21	gold quality
Ammon’s horn	UBERON:0001954	45.09	gold quality
brain	UBERON:0000955	44.49	gold quality
sural nerve	UBERON:0015488	43.21	gold quality
liver	UBERON:0002107	42.95	gold quality
right lobe of liver	UBERON:0001114	42.41	silver quality
substantia nigra	UBERON:0002038	41.27	gold quality
bone marrow cell	CL:0002092	40.05	gold quality
cerebellum	UBERON:0002037	38.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	38.71	gold quality
cerebellar cortex	UBERON:0002129	38.68	gold quality
cerebellar hemisphere	UBERON:0002245	38.47	gold quality
ganglionic eminence	UBERON:0004023	37.30	gold quality
putamen	UBERON:0001874	36.73	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
caudate nucleus	UBERON:0001873	35.93	gold quality
bone marrow	UBERON:0002371	34.91	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.20

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 11)

• Genomic duplications encompassing BHLHA9 are associated with SHFLD and non-Mendelian inheritance characterised by a high degree of non-penetrance with sex bias. (PMID:22147889)
• BHLHA9 gene contribute to the phenotype of small 17p13.3 chromosomal duplication in Miller-Dieker syndrome (PMID:23035971)
• Here, we report on 13 new families presenting with ectrodactyly and harboring a BHLHA9 duplication. (PMID:23790188)
• this is the first study revealing the underlying genetic factor for the development of GWC, and demonstrating the presence of triplications involving BHLHA9 (PMID:25351291)
• BHLHA9 is identified as an essential player in the regulatory network governing limb morphogenesis in humans. (PMID:25466284)
• Founder triplication of BHLHA9 is associated with femoral-tibial-digital malformations. (PMID:26333411)
• A novel insertion and deletion mutation in the BHLHA9 causes polydactyly and mesoaxial synostotic syndactyly with phalangeal reduction. (PMID:30107244)
• This is the second report providing evidence of association of polydactyly with Mesoaxial synostotic syndactyly caused by frameshift variant in the gene BHLHA9. The present molecular investigation will support genetic counselling of the local population carrying diseased variants. (PMID:31152918)
• BHLHA9 duplication causing split hand/foot malformation with long bone deficiency. (PMID:31200655)
• Whole exome sequencing identified a novel frameshift variant in the BHLHA9 in an Iranian family with mesoaxial synostotic syndactyly. (PMID:34272776)
• SHFLD3 phenotypes caused by 17p13.3 triplication/ duplication encompassing Fingerin (BHLHA9) invariably. (PMID:36028842)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	bhlha9	ENSDARG00000103981
mus_musculus	Bhlha9	ENSMUSG00000044243
rattus_norvegicus	Bhlha9	ENSRNOG00000022232
drosophila_melanogaster	twi	FBGN0003900
drosophila_melanogaster	HLH54F	FBGN0022740
drosophila_melanogaster	Hand	FBGN0032209
drosophila_melanogaster	CG33557	FBGN0053557
caenorhabditis_elegans		WBGENE00001953

Paralogs (13): HAND1 (ENSG00000113196), TCF21 (ENSG00000118526), TWIST1 (ENSG00000122691), TCF15 (ENSG00000125878), FERD3L (ENSG00000146618), TCF23 (ENSG00000163792), HAND2 (ENSG00000164107), PTF1A (ENSG00000168267), MSC (ENSG00000178860), FIGLA (ENSG00000183733), TWIST2 (ENSG00000233608), SCX (ENSG00000260428), TCF24 (ENSG00000261787)

Protein

Protein identifiers

Class A basic helix-loop-helix protein 9 — Q7RTU4 (reviewed: Q7RTU4)

Alternative names: Class F basic helix-loop-helix factor 42

All UniProt accessions (1): Q7RTU4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor, which play a role in limb development. Is an essential player in the regulatory network governing transcription of genes implicated in limb morphogenesis.

Subunit / interactions. Heterodimer. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with TCF3, TCF4, and TCF12.

Subcellular location. Nucleus. Cytoplasm.

Disease relevance. Split-hand/foot malformation with long bone deficiency 3 (SHFLD3) [MIM:612576] A disease characterized by the association of split-hand/foot malformation with long bone deficiency involving the tibia and fibula. Split-hand/foot malformation is a limb malformation involving the central rays of the autopod. Phenotypic expression is extremely variable between and within families, and even between limbs of a single patient, ranging from syndactyly and oligodactyly to the most severe monodactyly with only a single phalanx. Limb features include median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Disease susceptibility may be associated with variants affecting the gene represented in this entry. A copy number variation (CNV) resulting in BHLHA9 duplications is a necessary but not sufficient susceptibility factor for Split-hand/foot malformation with long bone deficiency, a highly variable phenotype with reduced penetrance, particularly in females. Syndactyly, mesoaxial synostotic, with phalangeal reduction (MSSD) [MIM:609432] An autosomal recessive, non-syndromic digit anomaly characterized by mesoaxial osseous synostosis at a metacarpal level, reduction of one or more phalanges, hypoplasia of distal phalanges of preaxial and postaxial digits, clinodactyly of fifth fingers, and preaxial fusion of toes. The disease is caused by variants affecting the gene represented in this entry. Camptosynpolydactyly, complex (CCSPD) [MIM:607539] An autosomal recessive disorder characterized by hand and foot deformities consisting of polydactyly with digits arising from the dorsum of hands, syn- and camptodactyly of some fingers, soft tissue syndactyly of first and second toes, and dysplastic nails. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_001157877* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050283	E-box_TF_Regulators	Family

Pfam: PF00010

UniProt features (9 total): sequence variant 4, region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTU4-F1	66.46	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, HP_ABNORMALITY_OF_THE_OUTER_EAR, HP_ABNORMAL_DIAPHYSIS_MORPHOLOGY, HP_SINGLE_TRANSVERSE_PALMAR_CREASE, HP_ABNORMAL_PALMAR_DERMATOGLYPHICS, HP_PTERYGIUM, HP_BRACHYDACTYLY

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), developmental process (GO:0032502)

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
biological_process	1
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BHLHA9	TRARG1	Q8IXB3	921
BHLHA9	PITPNA	Q00169	834
BHLHA9	YWHAE	P29360	807
BHLHA9	TIMM22	Q9Y584	770
BHLHA9	SCARF1	Q14162	759
BHLHA9	PAFAH1B1	P43034	757
BHLHA9	CRK	P46108	646
BHLHA9	C4orf46	Q504U0	587
BHLHA9	RD3L	P0DJH9	573
BHLHA9	ASCL5	Q7RTU5	532
BHLHA9	LMBR1	Q8WVP7	519
BHLHA9	ZNF684	Q5T5D7	511
BHLHA9	OR8B4	Q96RC9	500
BHLHA9	OR5AP2	Q8NGF4	476
BHLHA9	FBXO48	Q5FWF7	472

IntAct

37 interactions, top by confidence:

A	B	Type	Score
BHLHA9	PPP1R12C	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
KRT31	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
BHLHA9	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
BHLHA9	BCL2L2	psi-mi:“MI:0915”(physical association)	0.560
SAT1	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
POMC	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
STK16	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
	BHLHA9	psi-mi:“MI:0915”(physical association)	0.560
BHLHA9	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
BHLHA9	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
BHLHA9	PPP1R12C	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	TFIP11	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	KIAA0753	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	GOLGA6L9	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	KRT31	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	NECAB1	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9		psi-mi:“MI:0915”(physical association)	0.000
BCL2L2	BHLHA9	psi-mi:“MI:0915”(physical association)	0.000
SAT1	BHLHA9	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	POMC	psi-mi:“MI:0915”(physical association)	0.000
STK16	BHLHA9	psi-mi:“MI:0915”(physical association)	0.000
BHLHA9	MCRS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid), BHLHA9 (Two-hybrid)

ESM2 similar proteins: A0A0U1RR11, A0A0U1RRI6, A6NCS6, A6NJG2, B0BN44, D3YXK1, E9PY61, E9Q0B3, F5H4A9, O00220, O00221, P09038, P0DPI3, P22083, P98077, Q08AU9, Q2M2W7, Q2M3V2, Q2TBI2, Q5F267, Q5FW56, Q5IS69, Q5R866, Q5T4W7, Q5TM52, Q5U4P2, Q5VTJ3, Q659K9, Q673H1, Q69ZB3, Q6AYE8, Q6IPT2, Q6PJ61, Q7RTU4, Q7TSX9, Q7YR31, Q80SU3, Q86SH2, Q86Y97, Q8NBR0

Diamond homologs: A3KNX5, O13125, O13126, O57598, P48985, P48987, P70661, Q10574, Q4ZHW1, Q5RJB0, Q7RTS1, Q7RTU4, Q7ZSX3, Q8AW52, Q8N100, Q923Z4, Q96RJ6, Q9QX98, Q9VGJ5, A8E5T6, B6VQA1, O09029, O09105, O16867, O35437, O42202, O42606, O43680, O60682, O88940, O96642, P12980, P13903, P26687, P46581, P48986, P59101, P70447, P70562, P70595

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	5
Uncertain significance	67
Likely benign	25
Benign	3

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1328439	GRCh37/hg19 17p13.3(chr17:1145231-1499243)x1	Pathogenic
162065	NM_001164405.2(BHLHA9):c.211A>G (p.Asn71Asp)	Pathogenic
162067	NM_001164405.2(BHLHA9):c.224G>T (p.Arg75Leu)	Pathogenic
1695397	Single allele	Pathogenic
253567	GRCh37/hg19 17p13.3(chr17:1145504-1445005)x3	Pathogenic
3063489	GRCh37/hg19 17p13.3(chr17:1139864-1703566)x3	Pathogenic
3063491	GRCh37/hg19 17p13.3(chr17:1165481-1305567)x1	Pathogenic
394875	GRCh37/hg19 17p13.3(chr17:1114083-1784979)x1	Pathogenic
4075969	GRCh37/hg19 17p13.3(chr17:1092318-1496540)x4	Pathogenic
4075971	GRCh37/hg19 17p13.3(chr17:1092258-1496540)x3	Pathogenic
4279461	GRCh37/hg19 17p13.3(chr17:1141153-1203450)x1	Pathogenic
4682914	GRCh37/hg19 17p13.3(chr17:1092566-1555778)x3	Pathogenic
162066	NM_001164405.2(BHLHA9):c.218G>C (p.Arg73Pro)	Likely pathogenic
253164	NC_000017.11:g.1270783_1270784delinsTT	Likely pathogenic
3065871	NM_001164405.2(BHLHA9):c.218G>T (p.Arg73Leu)	Likely pathogenic
441930	GRCh37/hg19 17p13.3(chr17:1165433-1277056)x1	Likely pathogenic
980145	GRCh37/hg19 17p13.3(chr17:1121817-1277056)x3	Likely pathogenic

SpliceAI

66 predictions. Top by Δscore:

Variant	Effect	Δscore
17:1270882:C:G	donor_gain	0.6600
17:1270627:G:GT	donor_gain	0.6400
17:1270857:C:T	donor_gain	0.6200
17:1270602:G:GT	donor_gain	0.6000
17:1270583:GAC:G	donor_gain	0.5500
17:1270624:G:GT	donor_gain	0.5500
17:1270728:G:GT	donor_gain	0.5200
17:1271171:G:GT	donor_gain	0.5200
17:1270615:G:GT	donor_gain	0.4900
17:1271171:G:T	donor_gain	0.4800
17:1270890:G:GT	donor_gain	0.4600
17:1270965:G:GT	donor_gain	0.4300
17:1270843:C:T	donor_gain	0.4100
17:1270606:G:GT	donor_gain	0.3600
17:1271302:G:T	donor_gain	0.3400
17:1270603:A:T	donor_gain	0.3300
17:1271069:C:CA	donor_gain	0.3300
17:1271340:G:GA	acceptor_gain	0.3300
17:1271279:CGAGG:C	acceptor_gain	0.3200
17:1271413:G:GT	donor_gain	0.3200
17:1271301:G:GT	donor_gain	0.3100
17:1270782:G:GT	donor_gain	0.3000
17:1270921:GTCC:G	donor_gain	0.3000
17:1270922:TCCT:T	donor_gain	0.3000
17:1271417:G:GT	donor_gain	0.3000
17:1270750:TCC:T	donor_gain	0.2900
17:1270891:G:T	donor_gain	0.2900
17:1271374:GC:G	donor_gain	0.2900
17:1271390:G:GT	donor_gain	0.2900
17:1271399:G:GT	donor_gain	0.2900

AlphaMissense

1460 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:1270816:T:C	F85L	0.999
17:1270818:C:A	F85L	0.999
17:1270818:C:G	F85L	0.999
17:1270872:G:C	K103N	0.999
17:1270872:G:T	K103N	0.999
17:1270785:G:C	E74D	0.998
17:1270785:G:T	E74D	0.998
17:1270792:C:A	R77S	0.998
17:1270817:T:C	F85S	0.998
17:1270786:C:A	R75S	0.997
17:1270796:T:C	I78T	0.997
17:1270809:C:A	N82K	0.997
17:1270809:C:G	N82K	0.997
17:1270868:C:T	S102F	0.997
17:1270870:A:G	K103E	0.997
17:1270871:A:T	K103M	0.997
17:1270883:T:A	L107Q	0.997
17:1270883:T:C	L107P	0.997
17:1270784:A:T	E74V	0.996
17:1270808:A:T	N82I	0.996
17:1270816:T:A	F85I	0.996
17:1270870:A:C	K103Q	0.996
17:1270776:C:A	N71K	0.995
17:1270776:C:G	N71K	0.995
17:1270783:G:A	E74K	0.995
17:1270828:C:A	R89S	0.995
17:1270891:G:C	A110P	0.995
17:1270793:G:C	R77P	0.994
17:1270817:T:G	F85C	0.994
17:1270822:G:C	A87P	0.994

dbSNP variants (sampled 300 via entrez): RS1000204130 (17:1269695 G>A), RS1000848355 (17:1268509 C>T), RS1000956822 (17:1269731 A>G), RS1001800152 (17:1271438 C>A,T), RS1002397924 (17:1270578 G>A,C), RS1004056867 (17:1270052 C>A), RS1006018746 (17:1269081 C>T), RS1006490119 (17:1269354 T>G), RS1007328605 (17:1269694 T>C), RS1007471985 (17:1269858 G>C), RS1007599007 (17:1270519 G>A,C,T), RS1008519083 (17:1271038 A>G), RS1008587272 (17:1270810 G>A,C), RS1009011589 (17:1269301 C>A), RS1009984820 (17:1271227 G>A,C,T)

Disease associations

OMIM: gene MIM:615416 | disease phenotypes: MIM:607539, MIM:609432, MIM:613215, MIM:612576

GenCC curated gene-disease

Disease	Classification	Inheritance
mesoaxial synostotic syndactyly with phalangeal reduction	Definitive	Autosomal recessive
tibial aplasia-ectrodactyly syndrome	Strong	Autosomal dominant
split-hand/foot malformation with long bone deficiency 1	Limited	Unknown
Camptosynpolydactyly, complex	Limited	Autosomal recessive

Mondo (6): Camptosynpolydactyly, complex (MONDO:0011853), mesoaxial synostotic syndactyly with phalangeal reduction (MONDO:0012271), chromosome 17p13.3 duplication syndrome (MONDO:0013182), chromosome 17P13.3, telomeric, duplication syndrome (MONDO:0012944), split-hand/foot malformation with long bone deficiency 1 (MONDO:0007332), tibial aplasia-ectrodactyly syndrome (MONDO:0018050)

Orphanet (3): Mesoaxial synostotic syndactyly with phalangeal reduction (Orphanet:157801), 17p13.3 microduplication syndrome (Orphanet:217385), Tibial aplasia-ectrodactyly syndrome (Orphanet:3329)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000396	Overfolded helix
HP:0000954	Single transverse palmar crease
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001162	Postaxial hand polydactyly
HP:0001171	Split hand
HP:0001177	Preaxial hand polydactyly
HP:0001376	Limitation of joint mobility
HP:0001539	Omphalocele
HP:0001770	Toe syndactyly
HP:0001792	Small nail
HP:0002164	Nail dysplasia
HP:0002823	Abnormal femur morphology
HP:0002980	Femoral bowing
HP:0002991	Abnormal fibula morphology
HP:0003038	Fibular hypoplasia
HP:0003097	Short femur
HP:0003577	Congenital onset
HP:0004058	Hand monodactyly
HP:0004209	Clinodactyly of the 5th finger
HP:0004279	Short palm
HP:0004691	2-3 toe syndactyly
HP:0005048	Synostosis of carpal bones
HP:0005772	Aplasia/Hypoplasia of the tibia
HP:0006097	3-4 finger osseus syndactyly
HP:0006101	Finger syndactyly
HP:0006443	Patellar aplasia
HP:0006495	Aplasia/Hypoplasia of the ulna
HP:0008362	Aplasia/Hypoplasia of the hallux

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
C564383	Camptosynpolydactyly, Complex (supp.)
C567705	Chromosome 17p13.3 Duplication Syndrome (supp.)
C567245	Split-Hand-Foot Malformation With Long Bone Deficiency 3 (supp.)
C536425	Split-hand-foot malformation with long bone deficiency (supp.)
C563721	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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