ELP4

Summary

ELP4 (elongator acetyltransferase complex subunit 4, HGNC:1171) is a protein-coding gene on chromosome 11p13, encoding Elongator complex protein 4 (Q96EB1). Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). It is a selective cancer dependency (DepMap: 42.5% of cell lines).

This gene encodes a component of the six subunit elongator complex, a histone acetyltransferase complex that associates directly with RNA polymerase II during transcriptional elongation. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. This gene has also been associated with Rolandic epilepsy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 26610 — RefSeq curated summary.

At a glance

• Gene–disease (curated): aniridia 2 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 283 total — 25 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 8
• Cancer dependency (DepMap): dependent in 42.5% of screened cell lines
• MANE Select transcript: NM_019040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1171
Approved symbol	ELP4
Name	elongator acetyltransferase complex subunit 4
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	PAXNEB
Ensembl gene	ENSG00000109911
Ensembl biotype	protein_coding
OMIM	606985
Entrez	26610

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 21 protein_coding, 6 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000350638, ENST00000379163, ENST00000395934, ENST00000474374, ENST00000638184, ENST00000638317, ENST00000638347, ENST00000638376, ENST00000638384, ENST00000638482, ENST00000638508, ENST00000638764, ENST00000638828, ENST00000638917, ENST00000638984, ENST00000639097, ENST00000639182, ENST00000639570, ENST00000639878, ENST00000640059, ENST00000640081, ENST00000640231, ENST00000640342, ENST00000640379, ENST00000640533, ENST00000640790, ENST00000640921, ENST00000640954, ENST00000640961, ENST00000919838, ENST00000948241, ENST00000948242, ENST00000948243

RefSeq mRNA: 3 — MANE Select: NM_019040 NM_001288725, NM_001288726, NM_019040

CCDS: CCDS73271, CCDS73272, CCDS7875

Canonical transcript exons

ENST00000640961 — 10 exons

Exon	Start	End
ENSE00000708312	31594770	31594901
ENSE00000988255	31539662	31539783
ENSE00001004104	31520056	31520091
ENSE00003488007	31603768	31603907
ENSE00003559973	31650115	31650221
ENSE00003580122	31632217	31632405
ENSE00003616769	31627110	31627194
ENSE00003631647	31647741	31647849
ENSE00003804362	31509767	31510007
ENSE00003804367	31783393	31790324

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 91.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4030 / max 787.2847, expressed in 1805 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113596	18.9853	1805
113600	1.4055	227
113599	1.0395	283
113598	0.7682	159
113597	0.1672	69
113602	0.0221	12
113601	0.0153	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	91.77	gold quality
calcaneal tendon	UBERON:0003701	90.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.37	gold quality
secondary oocyte	CL:0000655	89.09	gold quality
islet of Langerhans	UBERON:0000006	88.08	gold quality
ganglionic eminence	UBERON:0004023	87.96	gold quality
oocyte	CL:0000023	87.89	gold quality
cerebellar hemisphere	UBERON:0002245	87.38	gold quality
cerebellar cortex	UBERON:0002129	87.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.03	gold quality
tendon	UBERON:0000043	85.68	gold quality
cerebellum	UBERON:0002037	85.45	gold quality
frontal pole	UBERON:0002795	85.32	gold quality
palpebral conjunctiva	UBERON:0001812	84.67	gold quality
embryo	UBERON:0000922	84.61	gold quality
adrenal tissue	UBERON:0018303	84.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.94	gold quality
pancreas	UBERON:0001264	83.63	gold quality
rectum	UBERON:0001052	83.37	gold quality
body of pancreas	UBERON:0001150	83.13	gold quality
mucosa of transverse colon	UBERON:0004991	83.01	gold quality
popliteal artery	UBERON:0002250	82.95	gold quality
tibial artery	UBERON:0007610	82.94	gold quality
esophagus squamous epithelium	UBERON:0006920	82.73	gold quality
muscle of leg	UBERON:0001383	82.43	gold quality
caudate nucleus	UBERON:0001873	82.31	gold quality
esophagus mucosa	UBERON:0002469	82.30	gold quality
amygdala	UBERON:0001876	82.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	82.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ELP4, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-190B-3P	99.33	68.29	1382

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 42.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• Data suggest that a non-coding mutation in ELP4 impairs brain-specific Elongator-mediated interaction of genes implicated in brain development, resulting in susceptibility to seizures and neurodevelopmental disorders. (PMID:19172991)
• No association of SNPs in the ELP4 gene was detected in rolandic epilepsy patients. (PMID:24995671)
• Results show no difference in BDNF and ELP4 genotype frequencies between benign epilepsy with centrotemporal spikes patients and controls; haplotype analysis also revealed no statistical difference (PMID:25301525)
• Our results suggest that ELP4 deletions are highly likely to be pathogenic, predisposing to a range of neurodevelopmental phenotypes from ASD to language impairment and epilepsy. (PMID:26010655)
• Elongator activated migration and invasion of hepatocellular carcinoma cells by promoting the expression of MMP-2 and MMP-9 through the PI3K/AKT signaling pathway (PMID:29805303)
• ELP4 rs986527 polymorphism affected the incidence of clinical symptoms and the levels of TNF-alpha and IL-1beta in patients with intracranial Arachnoid Cysts. (PMID:31743616)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	elp4	ENSDARG00000008852
mus_musculus	Elp4	ENSMUSG00000027167
rattus_norvegicus	AABR07053185.1	ENSRNOG00000004787
rattus_norvegicus	Elp4-ps1	ENSRNOG00000016146
drosophila_melanogaster	Elp4	FBGN0031711
caenorhabditis_elegans		WBGENE00016128

Protein

Protein identifiers

Elongator complex protein 4 — Q96EB1 (reviewed: Q96EB1)

Alternative names: PAX6 neighbor gene protein

All UniProt accessions (22): Q96EB1, A0A1W2PNF7, A0A1W2PNW2, A0A1W2PNY4, A0A1W2PNY5, A0A1W2PP47, A0A1W2PP49, A0A1W2PPP6, A0A1W2PPR3, A0A1W2PQ05, A0A1W2PQA7, A0A1W2PQW5, A0A1W2PQZ6, A0A1W2PR08, A0A1W2PRF0, A0A1W2PRF5, A0A1W2PRJ0, A0A1W2PS44, A0A1W2PS93, A0A1X7SBS0, E9PPJ9, G5E9D4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.

Subunit / interactions. Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed.

Disease relevance. Aniridia 2 (AN2) [MIM:617141] A form of aniridia, a congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time. The disease is caused by variants affecting the gene represented in this entry. A disease-causing mutation is located in intron 9 of ELP4. The mutation does not alter normal ELP4 expression and function, but disrupts a long-range cis-regulatory element of PAX6 expression, known as SIMO. SIMO is contained within ELP4 intron 9 and located 150 kb downstream of PAX6.

Pathway. tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis.

Similarity. Belongs to the ELP4 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96EB1-1	1	yes
Q96EB1-2	2
Q96EB1-3	3

RefSeq proteins (3): NP_001275654, NP_001275655, NP_061913* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008728	Elongator_complex_protein_4	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF05625

UniProt features (5 total): splice variant 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EB1-F1	74.49	0.39

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 140 (showing top): GCANCTGNY_MYOD_Q6, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, CAGCTG_AP4_Q5, NKX61_01, GOBP_TRANSLATION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, OCT1_06, OCT1_07, HAND1E47_01, CART1_01, GOBP_TRNA_PROCESSING

GO Biological Process (4): tRNA wobble uridine modification (GO:0002098), regulation of transcription by RNA polymerase II (GO:0006357), regulation of translation (GO:0006417), tRNA processing (GO:0008033)

GO Molecular Function (2): protein binding (GO:0005515), phosphorylase kinase regulator activity (GO:0008607)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), transcription elongation factor complex (GO:0008023), elongator holoenzyme complex (GO:0033588), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chromatin modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tRNA wobble base modification	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
RNA processing	1
tRNA metabolic process	1
binding	1
phosphorylase kinase activity	1
protein kinase regulator activity	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
nuclear protein-containing complex	1
intracellular protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELP4	ELP5	Q8TE02	991
ELP4	ELP6	Q0PNE2	988
ELP4	ELP1	O95163	987
ELP4	ELP3	Q9H9T3	972
ELP4	DCDC1	P59894	926
ELP4	IMMP1L	Q96LU5	921
ELP4	DNAJC24	Q6P3W2	915
ELP4	ELP2	Q6IA86	872
ELP4	MPPED2	Q15777	855
ELP4	PAX6	P26367	832
ELP4	KTI12	Q96EK9	800
ELP4	DPH3	Q96FX2	780
ELP4	CTU1	Q7Z7A3	716
ELP4	MOCS3	O95396	645
ELP4	URM1	Q9BTM9	645

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ELP3	ELP1	psi-mi:“MI:0914”(association)	0.840
ELP1	ELP2	psi-mi:“MI:0914”(association)	0.620
ELP4	ELP5	psi-mi:“MI:0915”(physical association)	0.620
ELP4	ELP1	psi-mi:“MI:0914”(association)	0.600
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
PIPOX	ZNF217	psi-mi:“MI:0914”(association)	0.530
ELP1	ELP5	psi-mi:“MI:0914”(association)	0.460
ELP5	ELP1	psi-mi:“MI:0914”(association)	0.460
ELP4	BAZ2A	psi-mi:“MI:0915”(physical association)	0.400
ELP4	ELP5	psi-mi:“MI:0915”(physical association)	0.400
ELP4	PB1	psi-mi:“MI:0915”(physical association)	0.370
ELP4	HSPA8	psi-mi:“MI:0914”(association)	0.350
ELP6	ZBTB25	psi-mi:“MI:0914”(association)	0.350
ELP3	ACACB	psi-mi:“MI:0914”(association)	0.350
SLC26A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
SLC32A1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SLC8B1	GAA	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (91): ELP4 (Affinity Capture-RNA), ELP4 (Affinity Capture-MS), ELP4 (Affinity Capture-MS), ELP2 (Co-fractionation), SF3B3 (Co-fractionation), ELP4 (Affinity Capture-Western), ELP4 (Affinity Capture-MS), ELP4 (Proximity Label-MS), ELP4 (Affinity Capture-MS), ELP4 (Affinity Capture-MS), ELP4 (Affinity Capture-MS), ELP4 (Negative Genetic), ELP4 (Negative Genetic), ELP4 (Negative Genetic), FAM98B (Negative Genetic)

ESM2 similar proteins: A0A1S4BZI5, A0A1S4CB73, A2X0Q3, A2XFC1, A2Y8B9, A2YTP9, E0ZS45, F4JVN6, K7WIZ6, O23617, O64815, O80738, P47823, Q01IJ3, Q0DGU2, Q0DSV9, Q0E3I9, Q0WUI9, Q10P67, Q10S55, Q13144, Q2QTL0, Q42381, Q5VS72, Q5Z9I2, Q5ZPI9, Q5ZPV8, Q69S81, Q6ESI7, Q6L5F5, Q6PBN5, Q6UTZ2, Q6YXZ7, Q6ZD95, Q7X745, Q7Y021, Q7Y0S0, Q84TQ7, Q8GWT4, Q8L7N4

Diamond homologs: Q2TBH6, Q54XS0, Q566Y1, Q5XG58, Q96EB1, Q9ER73, Q9VMQ7, Q60ZM2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ELP4	“form complex”	“Elongator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HATs acetylate histones	5	20.9×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of translation	5	52.1×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	6
Uncertain significance	146
Likely benign	31
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
120328	NM_019040.5(ELP4):c.1143+14176C>A	Pathogenic
1458968	NC_000011.9:g.(?31804921)(31812428_?)del	Pathogenic
151275	GRCh38/hg38 11p13(chr11:31600532-32122801)x3	Pathogenic
1808645	GRCh37/hg19 11p13(chr11:31794997-31822354)x1	Pathogenic
194162	NM_001368894.2(PAX6):c.1280_1284dup (p.Ser429fs)	Pathogenic
2422793	NC_000011.9:g.(?31625295)(31822424_?)del	Pathogenic
2422796	NC_000011.9:g.(?31804921)(31816356_?)del	Pathogenic
2443076	NM_001368894.2(PAX6):c.1277_1284dup (p.Ser429fs)	Pathogenic
253534	GRCh37/hg19 11p13(chr11:31802384-31825698)x1	Pathogenic
267192	NC_000011.8:g.31199000_31914000del715001	Pathogenic
3391912	GRCh37/hg19 11p13(chr11:31504814-31901663)x1	Pathogenic
376756	GRCh37/hg19 11p13(chr11:31760458-31823847)x1	Pathogenic
379272	NM_001368894.2(PAX6):c.1226-2A>G	Pathogenic
4070940	Single allele	Pathogenic
529895	NC_000011.10:g.(?31789934)(31806411_?)del	Pathogenic
565298	NM_001604.5(PAX6):c.(10+1_11-1)(1311?)del	Pathogenic
583750	NC_000011.9:g.(?31284590)(32456911_?)del	Pathogenic
58860	GRCh38/hg38 11p13(chr11:31500417-31539732)x1	Pathogenic
58886	GRCh38/hg38 11p13(chr11:31528093-31807593)x1	Pathogenic
58887	GRCh38/hg38 11p13(chr11:31765618-31792086)x1	Pathogenic
692032	NM_001368894.2(PAX6):c.1309dup (p.Ter437LeuextTer?)	Pathogenic
800478	NM_001368894.2(PAX6):c.1226-1G>C	Pathogenic
800479	NM_001368894.2(PAX6):c.1282dup (p.Met428fs)	Pathogenic
800480	NM_001368894.2(PAX6):c.1294_1308delinsACAGTAAA (p.Trp432fs)	Pathogenic
800481	NM_001368894.2(PAX6):c.1295_1304del (p.Trp432fs)	Pathogenic
1328941	NM_019040.5(ELP4):c.886C>A (p.Leu296Ile)	Likely pathogenic
1328942	NM_019040.5(ELP4):c.272A>G (p.Tyr91Cys)	Likely pathogenic
2685404	GRCh37/hg19 11p13(chr11:31501986-31578568)x1	Likely pathogenic
3776221	NM_001368894.2(PAX6):c.1307del (p.Gln436fs)	Likely pathogenic
4784256	NM_001368894.2(PAX6):c.1238del (p.Pro413fs)	Likely pathogenic

SpliceAI

3570 predictions. Top by Δscore:

Variant	Effect	Δscore
11:31520048:A:AG	acceptor_gain	1.0000
11:31520049:T:G	acceptor_gain	1.0000
11:31520091:GGTT:G	donor_loss	1.0000
11:31520092:G:GG	donor_gain	1.0000
11:31520092:GTTA:G	donor_loss	1.0000
11:31539657:TACA:T	acceptor_loss	1.0000
11:31539657:TACAG:T	acceptor_gain	1.0000
11:31539658:ACAGA:A	acceptor_gain	1.0000
11:31539659:CA:C	acceptor_loss	1.0000
11:31539659:CAG:C	acceptor_gain	1.0000
11:31539660:A:AG	acceptor_gain	1.0000
11:31539660:AG:A	acceptor_loss	1.0000
11:31539660:AGA:A	acceptor_gain	1.0000
11:31539660:AGAG:A	acceptor_gain	1.0000
11:31539661:G:C	acceptor_gain	1.0000
11:31539661:G:GC	acceptor_gain	1.0000
11:31539661:GA:G	acceptor_gain	1.0000
11:31539661:GAGG:G	acceptor_gain	1.0000
11:31539661:GAGGA:G	acceptor_gain	1.0000
11:31539701:A:G	acceptor_gain	1.0000
11:31539779:TACAG:T	donor_loss	1.0000
11:31539780:ACAGG:A	donor_loss	1.0000
11:31539781:CAGG:C	donor_loss	1.0000
11:31539782:AGGTA:A	donor_loss	1.0000
11:31539784:G:GA	donor_loss	1.0000
11:31539785:T:G	donor_loss	1.0000
11:31583907:T:G	donor_gain	1.0000
11:31594765:CTTA:C	acceptor_loss	1.0000
11:31594767:TA:T	acceptor_loss	1.0000
11:31594768:A:AG	acceptor_gain	1.0000

AlphaMissense

2737 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:31594872:T:A	W162R	0.993
11:31594872:T:C	W162R	0.993
11:31594874:G:C	W162C	0.991
11:31594874:G:T	W162C	0.991
11:31650115:G:A	G346E	0.991
11:31632240:A:C	R254S	0.990
11:31632240:A:T	R254S	0.990
11:31594870:C:A	A161D	0.989
11:31650190:T:C	F371S	0.989
11:31509980:G:T	G66W	0.988
11:31539718:G:A	G106R	0.988
11:31539718:G:C	G106R	0.988
11:31594876:G:C	R163P	0.988
11:31632271:T:A	W265R	0.988
11:31632271:T:C	W265R	0.988
11:31594875:C:A	R163S	0.987
11:31647849:G:A	G346R	0.985
11:31647849:G:C	G346R	0.985
11:31509981:G:A	G66E	0.984
11:31650187:C:A	A370D	0.984
11:31650189:T:C	F371L	0.984
11:31650191:T:A	F371L	0.984
11:31650191:T:G	F371L	0.984
11:31539712:G:C	A104P	0.983
11:31783403:T:C	L385S	0.982
11:31632341:T:C	L288P	0.979
11:31647778:A:T	D322V	0.979
11:31632239:G:C	R254T	0.978
11:31632344:G:C	R289P	0.977
11:31632373:T:C	C299R	0.976

dbSNP variants (sampled 300 via entrez): RS1000004488 (11:31580196 C>A), RS1000004608 (11:31722500 G>T), RS1000033520 (11:31552891 G>A,C), RS1000035909 (11:31762777 A>C,G), RS1000050445 (11:31761282 G>A,T), RS1000059261 (11:31599655 T>G), RS1000073344 (11:31533657 G>A,C), RS1000082714 (11:31646293 C>T), RS1000092057 (11:31729956 A>G), RS1000097117 (11:31679501 A>G), RS1000106807 (11:31784381 T>C), RS1000109068 (11:31632898 T>A), RS1000133779 (11:31747598 A>G), RS1000141109 (11:31520338 C>T), RS1000145575 (11:31612730 A>C,G)

Disease associations

OMIM: gene MIM:606985 | disease phenotypes: MIM:617141, MIM:106210, MIM:120430, MIM:194072, MIM:604229, MIM:136520, MIM:148190, MIM:165550, MIM:136680, MIM:194070, MIM:194080

GenCC curated gene-disease

Disease	Classification	Inheritance
aniridia 2	Strong	Autosomal dominant
aniridia 1	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ocular dysgenesis caused by defects in PAX6 regulation	Moderate	AD

Mondo (16): aniridia 2 (MONDO:0014937), aniridia 1 (MONDO:0024507), coloboma of optic nerve (MONDO:0007354), PAX6-related ocular dysgenesis (MONDO:0800183), WAGR syndrome (MONDO:0008681), Peters anomaly (MONDO:0011414), autism spectrum disorder (MONDO:0005258), aniridia (MONDO:0019172), foveal hypoplasia 1 (MONDO:0007628), autosomal dominant keratitis (MONDO:0007848), coloboma (MONDO:0001476), pathologic nystagmus (MONDO:0004843), isolated optic nerve hypoplasia (MONDO:0008136), Frasier syndrome (MONDO:0007635), Wilms tumor 1 (MONDO:0008679)

Orphanet (16): Isolated aniridia (Orphanet:250923), Morning glory disc anomaly (Orphanet:35737), Coloboma of optic disc (Orphanet:98947), WAGR syndrome (Orphanet:893), Peters anomaly (Orphanet:708), Foveal hypoplasia-presenile cataract syndrome (Orphanet:2253), Autosomal dominant keratitis (Orphanet:2334), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), OBSOLETE: Ocular coloboma (Orphanet:194), Isolated optic nerve hypoplasia (Orphanet:637061), Denys-Drash syndrome (Orphanet:220), Frasier syndrome (Orphanet:347), Nephroblastoma (Orphanet:654), NON RARE IN EUROPE: Autism (Orphanet:106), OBSOLETE: Aniridia (Orphanet:77)

HPO phenotypes

8 total (10 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000518	Cataract
HP:0000526	Aniridia
HP:0000612	Iris coloboma
HP:0000646	Amblyopia
HP:0000648	Optic atrophy
HP:0001132	Lens subluxation
HP:0003577	Congenital onset
HP:0000588	Optic disc coloboma
HP:0000659	Peters anomaly

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002529_7	Glaucoma	2.000000e-08
GCST002763_15	Optic disc area	2.000000e-06
GCST002763_6	Optic disc area	6.000000e-10
GCST005839_4	Depression	1.000000e-09
GCST008550_26	Mental health study participation (completed survey)	2.000000e-08
GCST009462_110	Optic disc size	4.000000e-25
GCST009600_24	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-09
GCST009723_97	Vertical cup-disc ratio (adjusted for vertical disc diameter)	6.000000e-07
GCST009724_25	Vertical cup-disc ratio (multi-trait analysis)	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010130	health study participation
EFO:0006939	cup-to-disc ratio measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D015783	Aniridia	C11.250.060; C11.270.060; C11.941.375.060; C16.131.384.079; C16.320.290.078
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D030321	Denys-Drash Syndrome	C04.557.435.595.220; C04.588.945.947.535.585.220; C04.700.900.220; C12.050.351.875.253.096.562; C12.050.351.937.820.535.585.220; C12.050.351.968.419.473.585.220; C12.200.706.316.096.562; C12.200.758.820.750.585.220; C12.200.777.419.473.585.220; C12.800.316.096.562; C12.900.820.535.585.220; C12.950.419.473.585.220; C12.950.983.535.585.220; C16.131.939.316.096.562; C16.320.700.900.220; C19.391.119.096.562
D052159	Frasier Syndrome	C12.050.351.875.253.096.624; C12.050.351.968.419.780.750.500.500; C12.200.706.316.096.624; C12.200.777.419.780.750.500.500; C12.800.316.096.624; C12.950.419.780.750.500.500; C16.131.939.316.096.624; C16.320.306; C19.391.119.096.624; C23.550.291.500.906.500.500
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D017624	WAGR Syndrome	C04.557.435.595.950; C04.588.945.947.535.585.950; C04.700.900.950; C10.597.606.360.969; C11.250.060.950; C11.270.060.950; C11.941.375.060.950; C12.050.351.875.253.096.875; C12.050.351.937.820.535.585.950; C12.050.351.968.419.473.585.950; C12.200.706.316.096.875; C12.200.758.820.750.585.950; C12.200.777.419.473.585.950; C12.800.316.096.875; C12.900.820.535.585.950; C12.950.419.473.585.950; C12.950.983.535.585.950; C16.131.260.940; C16.131.384.079.950; C16.131.939.316.096.875; C16.320.180.940; C16.320.290.078.950; C16.320.700.900.950; C19.391.119.096.875
C536372	Aniridia, type 2 (supp.)
C535970	Coloboma of optic nerve (supp.)
C537022	Keratitis, hereditary (supp.)
C537884	Peters anomaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	8
Benzo(a)pyrene	affects methylation, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tretinoin	decreases expression, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
salinomycin	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder