ALX3

Summary

ALX3 (ALX homeobox 3, HGNC:449) is a protein-coding gene on chromosome 1p13.3, encoding Homeobox protein aristaless-like 3 (O95076). Transcriptional regulator with a possible role in patterning of mesoderm during development.

This gene encodes a nuclear protein with a homeobox DNA-binding domain that functions as a transcriptional regulator involved in cell-type differentiation and development. Preferential methylation of this gene’s promoter is associated with advanced-stage neuroblastoma tumors.

Source: NCBI Gene 257 — RefSeq curated summary.

At a glance

• Gene–disease (curated): frontorhiny (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 101 total — 11 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 53
• MANE Select transcript: NM_006492

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:449
Approved symbol	ALX3
Name	ALX homeobox 3
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000156150
Ensembl biotype	protein_coding
OMIM	606014
Entrez	257

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000647563, ENST00000649954

RefSeq mRNA: 1 — MANE Select: NM_006492 NM_006492

CCDS: CCDS819

Canonical transcript exons

ENST00000647563 — 4 exons

Exon	Start	End
ENSE00001024856	110061435	110061563
ENSE00001024858	110064587	110064903
ENSE00003837237	110070336	110070672
ENSE00003851138	110059870	110061041

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 80.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1560 / max 27.9737, expressed in 70 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13734	0.1046	50
13732	0.0514	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.85	gold quality
olfactory bulb	UBERON:0002264	69.41	gold quality
type B pancreatic cell	CL:0000169	69.34	gold quality
cervix squamous epithelium	UBERON:0006922	67.84	gold quality
triceps brachii	UBERON:0001509	66.34	gold quality
gluteal muscle	UBERON:0002000	66.23	gold quality
hair follicle	UBERON:0002073	65.06	gold quality
pancreatic ductal cell	CL:0002079	64.85	silver quality
diaphragm	UBERON:0001103	63.74	gold quality
epithelium of esophagus	UBERON:0001976	63.51	gold quality
periodontal ligament	UBERON:0008266	62.85	gold quality
heart right ventricle	UBERON:0002080	62.61	gold quality
esophagus squamous epithelium	UBERON:0006920	62.30	gold quality
male germ cell	CL:0000015	60.50	gold quality
cartilage tissue	UBERON:0002418	60.30	gold quality
quadriceps femoris	UBERON:0001377	60.29	gold quality
vastus lateralis	UBERON:0001379	60.04	gold quality
biceps brachii	UBERON:0001507	59.93	gold quality
sperm	CL:0000019	59.34	gold quality
squamous epithelium	UBERON:0006914	59.08	gold quality
postcentral gyrus	UBERON:0002581	58.53	gold quality
secondary oocyte	CL:0000655	58.28	gold quality
deltoid	UBERON:0001476	57.27	gold quality
mammary duct	UBERON:0001765	57.22	gold quality
nasal cavity epithelium	UBERON:0005384	57.14	gold quality
epithelium of mammary gland	UBERON:0003244	56.94	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	56.65	gold quality
seminal vesicle	UBERON:0000998	56.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	56.57	gold quality
inferior olivary complex	UBERON:0002127	56.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
ALX3
INS
SST

JASPAR motifs

Motif	Name	Family
MA0634.1	ALX3	Paired-related HD factors
MA0634.2	ALX3	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): ALX3, TCF3, TWIST1, USF1, USF2

miRNA regulators (miRDB)

30 targeting ALX3, 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-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-5009-5P	94.82	63.89	775
HSA-MIR-8058	94.76	63.41	632
HSA-MIR-6090	91.01	62.65	222

Literature-anchored findings (GeneRIF, showing 9)

• The lack of a chromosome 1-derived fragment of ALX3 in restriction landmark genomic scanning and virtual genome scans of neuroblastomas is attributable to hypermethylation. (PMID:11807986)
• Rat Alx3 undergoes restrictive or permissive interactions with nuclear proteins that determine its binding to and transactivation from TAAT target sites selected in a cell-specific manner. (PMID:15226305)
• Alx3 participates in the regulation of insulin gene expression in pancreatic beta-cells. (PMID:16825292)
• Chromatin immunoprecipitation assays indicated that Alx3 in mouse pancreatic islets occupies the promoter of the mouse insulin genes. (PMID:16825292)
• ALX3 is essential for normal facial development in humans and that deficiency causes a clinically recognizable phenotype, which we term frontorhiny. (PMID:19409524)
• We report a novel Y214X mutation in ALX3 in frontorhiny. (PMID:22106187)
• Exclusion of mutations in ALX3 gene in patients with the syndrome of frontonasal dysgenesis, callosal agenesis, basal encephalocele, and eye anomalies (PMID:22496059)
• Genome scan using 250k Nsp1 array followed by exome and Sanger sequence analysis revealed a novel homozygous nonsense variant (c.604C>T, p.Gln202*) in the ALX3 gene resulting in frontorhiny in the family. This is the first mutation in the ALX3 gene, underlying frontorhiny, in Pakistani population. (PMID:29215096)
• Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A. (PMID:34266408)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Alx3	ENSMUSG00000014603
rattus_norvegicus	Alx3	ENSRNOG00000018290

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Homeobox protein aristaless-like 3 — O95076 (reviewed: O95076)

Alternative names: Proline-rich transcription factor ALX3

All UniProt accessions (2): O95076, A0A3B3IS30

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator with a possible role in patterning of mesoderm during development.

Subcellular location. Nucleus.

Disease relevance. Frontonasal dysplasia 1 (FND1) [MIM:136760] The term frontonasal dysplasia describes an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism; broadening of the nasal root; median facial cleft affecting the nose and/or upper lip and palate; unilateral or bilateral clefting of the alae nasi; lack of formation of the nasal tip; anterior cranium bifidum occultum; a V-shaped or widow’s peak frontal hairline. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (1): NP_006483* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050649	Paired_Homeobox_TFs	Family

Pfam: PF00046

UniProt features (11 total): sequence variant 5, sequence conflict 3, 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-O95076-F1	62.90	0.18

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-1266738	Developmental Biology
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 232 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_HINDLIMB_MORPHOGENESIS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, AREB6_03, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GOBP_NEUROGENESIS, GOBP_FORELIMB_MORPHOGENESIS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_FORELIMB_MORPHOGENESIS, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS

GO Biological Process (8): regulation of transcription by RNA polymerase II (GO:0006357), pattern specification process (GO:0007389), embryonic forelimb morphogenesis (GO:0035115), embryonic hindlimb morphogenesis (GO:0035116), regulation of apoptotic process (GO:0042981), neuron development (GO:0048666), embryonic skeletal system morphogenesis (GO:0048704), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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 (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MITF-M-regulated melanocyte development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
embryonic limb morphogenesis	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
multicellular organism development	1
multicellular organismal process	1
forelimb morphogenesis	1
hindlimb morphogenesis	1
apoptotic process	1
regulation of programmed cell death	1
neuron differentiation	1
cell development	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic 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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALX3	SLC6A17	Q9H1V8	839
ALX3	MRTO4	Q9UKD2	827
ALX3	UBL4B	Q8N7F7	825
ALX3	RBM15	Q96T37	725
ALX3	TEX15	Q9BXT5	650
ALX3	LMX1A	Q8TE12	640
ALX3	PEPD	P12955	545
ALX3	TBX15	Q96SF7	522
ALX3	PAX6	P26367	495
ALX3	TBX4	P57082	470
ALX3	MIPOL1	Q8TD10	455
ALX3	MITF	O75030	438
ALX3	BMP5	P22003	435
ALX3	UBL4A	P11441	421
ALX3	SIX2	Q9NPC8	407

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ALX3	CRTAP	psi-mi:“MI:0914”(association)	0.530
	ALX3	psi-mi:“MI:0915”(physical association)	0.370
CCL1	ALX3	psi-mi:“MI:0915”(physical association)	0.370
PRRX1	ALX3	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): P3H2 (Affinity Capture-MS), NDUFAF7 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), CRTAP (Affinity Capture-MS), IKBIP (Affinity Capture-MS), MOCS3 (Affinity Capture-MS), SUPT16H (Affinity Capture-MS), C18orf25 (Affinity Capture-MS), UBN2 (Affinity Capture-MS), PRKAR2B (Affinity Capture-MS), P3H1 (Affinity Capture-MS), MACF1 (Affinity Capture-MS), FTO (Affinity Capture-MS), P3H4 (Affinity Capture-MS), XPC (Affinity Capture-MS)

ESM2 similar proteins: A1YF16, A1YG93, A2RU54, A2T764, A5PKG8, A6NCS4, A6NMT0, A8MTQ0, O14813, O35602, O57601, O70137, O70584, O95076, P23683, P35548, P42580, P43687, P49640, P50223, P52946, P52947, P52950, P63156, P63157, P70061, P70354, P97436, P97503, Q03358, Q0P5C3, Q5NSW5, Q62066, Q62782, Q91V10, Q99801, Q9BZE3, Q9DED6, Q9ER42, Q9GK08

Diamond homologs: A0A1W2PPF3, A1YEY5, A1YFI3, A1YG57, A2T733, A2T7P4, A6NLW8, A6NNA5, F1NEA7, G5EBU4, G5EDS1, O18381, O35137, O35160, O42250, O43186, O43316, O43812, O54751, O70137, O73917, O75360, O75364, O95076, P09088, P0CJ85, P0CJ86, P0CJ87, P0CJ88, P0CJ89, P0CJ90, P21711, P22810, P26367, P26630, P29454, P32242, P32243, P34764, P34765

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	1
Uncertain significance	63
Likely benign	11
Benign	10

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1459387	NC_000001.10:g.(?110603355)(111147404_?)del	Pathogenic
2146917	NM_006492.3(ALX3):c.592C>T (p.Gln198Ter)	Pathogenic
3069203	NM_006492.3(ALX3):c.364C>T (p.Gln122Ter)	Pathogenic
3775899	NM_006492.3(ALX3):c.553C>T (p.Gln185Ter)	Pathogenic
3777753	ALX3, GLN202TER	Pathogenic
4642	NM_006492.3(ALX3):c.595-2A>T	Pathogenic
4643	NM_006492.3(ALX3):c.608A>G (p.Asn203Ser)	Pathogenic
4644	NM_006492.3(ALX3):c.502C>G (p.Leu168Val)	Pathogenic
4646	NM_006492.3(ALX3):c.543T>A (p.Tyr181Ter)	Pathogenic
4647	NM_006492.3(ALX3):c.578_581del (p.Thr193fs)	Pathogenic
4648	NM_006492.3(ALX3):c.586C>T (p.Arg196Trp)	Pathogenic
559851	NM_006492.3(ALX3):c.736_737del (p.Leu246fs)	Likely pathogenic

SpliceAI

586 predictions. Top by Δscore:

Variant	Effect	Δscore
1:110061430:CTTA:C	donor_loss	1.0000
1:110061433:A:AG	donor_loss	1.0000
1:110061434:C:A	donor_loss	1.0000
1:110064581:CCTCA:C	donor_loss	1.0000
1:110064583:TCA:T	donor_loss	1.0000
1:110064585:A:AT	donor_loss	1.0000
1:110064586:C:T	donor_loss	1.0000
1:110064902:AG:A	acceptor_gain	1.0000
1:110064904:C:CC	acceptor_gain	1.0000
1:110061433:A:AC	donor_gain	0.9900
1:110061434:C:CC	donor_gain	0.9900
1:110061559:CAGAC:C	acceptor_gain	0.9900
1:110064899:CTCAG:C	acceptor_gain	0.9900
1:110064900:TCAG:T	acceptor_gain	0.9900
1:110064901:CAG:C	acceptor_gain	0.9900
1:110064901:CAGC:C	acceptor_gain	0.9900
1:110064902:AGCTG:A	acceptor_loss	0.9900
1:110064904:C:A	acceptor_loss	0.9900
1:110064905:T:A	acceptor_loss	0.9900
1:110064909:A:AC	acceptor_gain	0.9900
1:110070338:T:A	donor_gain	0.9900
1:110061571:CAGGT:C	acceptor_gain	0.9800
1:110061575:T:C	acceptor_gain	0.9800
1:110061575:T:TC	acceptor_gain	0.9800
1:110064585:A:AC	donor_gain	0.9800
1:110064586:C:CC	donor_gain	0.9800
1:110064767:C:CT	acceptor_gain	0.9800
1:110064767:C:T	acceptor_gain	0.9800
1:110064907:CAA:C	acceptor_gain	0.9800
1:110064908:A:T	acceptor_gain	0.9800

AlphaMissense

2200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:110061537:C:A	K207N	1.000
1:110061537:C:G	K207N	1.000
1:110061543:T:A	R205S	1.000
1:110061543:T:G	R205S	1.000
1:110061544:C:G	R205T	1.000
1:110061547:C:G	R204P	1.000
1:110061548:G:T	R204S	1.000
1:110061549:G:C	N203K	1.000
1:110061549:G:T	N203K	1.000
1:110061550:T:A	N203I	1.000
1:110061550:T:C	N203S	1.000
1:110061550:T:G	N203T	1.000
1:110061551:T:C	N203D	1.000
1:110061551:T:G	N203H	1.000
1:110061555:G:C	F201L	1.000
1:110061555:G:T	F201L	1.000
1:110061556:A:C	F201C	1.000
1:110061556:A:G	F201S	1.000
1:110061557:A:C	F201V	1.000
1:110061557:A:G	F201L	1.000
1:110061557:A:T	F201I	1.000
1:110061558:C:A	W200C	1.000
1:110061558:C:G	W200C	1.000
1:110061560:A:G	W200R	1.000
1:110061560:A:T	W200R	1.000
1:110064606:A:G	L192P	1.000
1:110064624:A:G	L186P	1.000
1:110064648:G:T	P178H	1.000
1:110064649:G:A	P178S	1.000
1:110064651:T:C	Y177C	1.000

dbSNP variants (sampled 300 via entrez): RS1000171661 (1:110060504 T>TCAC), RS1000235982 (1:110069001 C>T), RS1000495180 (1:110067981 G>A), RS1001054566 (1:110067680 C>A,T), RS1001270841 (1:110059957 C>A,T), RS1001663532 (1:110069183 C>G), RS1001808848 (1:110063192 A>C), RS1001904846 (1:110069398 A>G), RS1001916056 (1:110070465 G>A), RS1002108661 (1:110064370 T>C), RS1002659450 (1:110070187 C>T), RS1002683853 (1:110061262 C>A,G,T), RS1003242578 (1:110064496 C>G,T), RS1003520915 (1:110072196 G>A), RS1003686818 (1:110059995 A>G)

Disease associations

OMIM: gene MIM:606014 | disease phenotypes: MIM:136760, MIM:616366

GenCC curated gene-disease

Disease	Classification	Inheritance
frontorhiny	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
frontorhiny	Definitive	AR

Mondo (2): frontorhiny (MONDO:0007636), developmental and epileptic encephalopathy, 32 (MONDO:0014607)

Orphanet (2): Frontorhiny (Orphanet:391474), Non-specific early-onset epileptic encephalopathy (Orphanet:442835)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000161	Median cleft upper lip
HP:0000175	Cleft palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000349	Widow’s peak
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000456	Bifid nasal tip
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000873	Diabetes insipidus
HP:0001156	Brachydactyly
HP:0001162	Postaxial hand polydactyly
HP:0001249	Intellectual disability
HP:0001274	Agenesis of corpus callosum
HP:0001566	Widely-spaced maxillary central incisors
HP:0001636	Tetralogy of Fallot
HP:0002000	Short columella
HP:0002084	Encephalocele
HP:0002650	Scoliosis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001524_21	Visceral adipose tissue/subcutaneous adipose tissue ratio	2.000000e-06
GCST009462_21	Optic disc size	1.000000e-09
GCST90000047_14	Age at first sexual intercourse	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Tretinoin	increases expression	2
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0A9	SEES3-1V human ALX3, clone1	Embryonic stem cell	Male
CVCL_A0B0	SEES3-1V human ALX3, clone2	Embryonic stem cell	Male
CVCL_A0B1	SEES3-1V human ALX3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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