EN2

Summary

EN2 (engrailed homeobox 2, HGNC:3343) is a protein-coding gene on chromosome 7q36.3, encoding Homeobox protein engrailed-2 (P19622).

Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the ’engrailed’ (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system.

Source: NCBI Gene 2020 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Disputed, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 89 total — 1 pathogenic
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001427

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3343
Approved symbol	EN2
Name	engrailed homeobox 2
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164778
Ensembl biotype	protein_coding
OMIM	131310
Entrez	2020

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000297375

RefSeq mRNA: 1 — MANE Select: NM_001427 NM_001427

CCDS: CCDS5940

Canonical transcript exons

ENST00000297375 — 2 exons

Exon	Start	End
ENSE00001087387	155458129	155459062
ENSE00001087388	155462371	155464831

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 88.48.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	88.48	gold quality
cerebellar hemisphere	UBERON:0002245	88.42	gold quality
cerebellum	UBERON:0002037	88.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.80	gold quality
cerebellar vermis	UBERON:0004720	85.13	gold quality
paraflocculus	UBERON:0005351	78.11	gold quality
endometrium epithelium	UBERON:0004811	69.17	gold quality
hair follicle	UBERON:0002073	65.13	gold quality
cranial nerve II	UBERON:0000941	64.79	silver quality
secondary oocyte	CL:0000655	63.21	gold quality
tongue squamous epithelium	UBERON:0006919	63.07	gold quality
buccal mucosa cell	CL:0002336	62.35	silver quality
hindlimb stylopod muscle	UBERON:0004252	60.52	gold quality
substantia nigra	UBERON:0002038	59.53	gold quality
midbrain	UBERON:0001891	57.76	gold quality
decidua	UBERON:0002450	56.55	gold quality
pancreatic ductal cell	CL:0002079	54.32	silver quality
amniotic fluid	UBERON:0000173	54.31	gold quality
endometrium	UBERON:0001295	54.22	gold quality
adult organism	UBERON:0007023	53.66	gold quality
endothelial cell	CL:0000115	51.90	gold quality
gastrocnemius	UBERON:0001388	51.42	gold quality
quadriceps femoris	UBERON:0001377	51.15	gold quality
left ovary	UBERON:0002119	51.10	gold quality
muscle of leg	UBERON:0001383	50.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	50.64	gold quality
ovary	UBERON:0000992	50.61	gold quality
muscle organ	UBERON:0001630	50.56	gold quality
sural nerve	UBERON:0015488	50.47	gold quality
frontal pole	UBERON:0002795	50.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
EN2
FGF8	Unknown
RPL7
WNT7B	Unknown

JASPAR motifs

Motif	Name	Family
MA0642.1	EN2	NK
MA0642.2	EN2	NK
MA0642.3	EN2	NK

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): BPTF, CTNNB1, EN2, PAX2, SMARCA1

miRNA regulators (miRDB)

139 targeting EN2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• In human, failure to form a mesencephalon and metencephalon, with cerebellar hypoplasia, results drom a mutation or deletion in EN2(Engrailed-2) gene. (PMID:11815869)
• EN2 exon 1 variant transmission disequilibrium test shows no association with autistic disorder nor association between language and stereotypic behaviour quantitative traits. (PMID:12525552)
• An association between a cerebellar patterning gene and autism spectrum disorder suggests a role for EN2 as a susceptibility locus and supports a neurodevelopmental defect hypothesis in the etiology of autism. (PMID:15024396)
• RNA interference studies suggest that EN2 expression is required for the maintenance of the transformed phenotype of a human breast tumor cell line (PMID:16007149)
• Loss and gain of function experiments firmly establish that En1/2 is a true survival factor for dopaminergic neurons in vivo. (PMID:17267560)
• Heterogeneous association between engrailed-2 and autism in the CPEA network (PMID:17948868)
• a preferential transmission of the rs3824068 A-allele to AUTISM affected offspring (PMID:17948901)
• Engrailed 2 gene is associated with autistic disorder in Chinese children. (PMID:18424904)
• The majority of regulated genes were down-regulated in engrailed-2 cerebella from transgenic mice, consistent with the known repressive function of Engrailed-2. (PMID:18562208)
• variations of the engrailed-2 gene are implicated in the development of young-onset Parkinson’s disease (PMID:19270442)
• The data of this study indicated that the A-C haplotype is functional and, together with the association and LD mapping results, supports EN2 as a likely autism susceptibility gene and the A-C haplotype as a possible risk allele. (PMID:19615670)
• Positive genetic correlation of EN2 with autism in the Indian population. (PMID:20050924)
• This study demonistrated that in Han chinese the association between the EN2 genetic polymorphism and autism. (PMID:20523082)
• findings show EN2 was expressed and secreted by prostate cancer (PC) cell lines and PC tissue but not by normal prostate tissue or stroma; presence of EN2 in urine was highly predictive of PC (PMID:21364037)
• The data demonstrates that the autism spectrum disorder-associated A-C intronic haplotype of the ENGRAILED2 gene is a transcriptional activator, and both CUX1 and NFIB mediate this activity. (PMID:22180456)
• The WNT2 gene and EN2 gene may act in concert to influence the language development in autism. (PMID:22522212)
• Normal EN-2 downregulation may not occur in some individuals with autism, such that the postnatal persistence of EN-2 overexpression may contribute to autism cerebellar abnormalities. (PMID:23423141)
• urinary EN2 has the potential to be a more sensitive and specific protein biomarker for non-muscle-invasive bladder cancer than currently available tests. (PMID:23434148)
• Urinary EN2 may be useful as a non-invasive early biomarker for prostate cancer detection in genetically high-risk individuals (PMID:23792811)
• Two patients with underdeveloped arcuate fasciculus had novel, nonsynonymous variants in MID1 and EN2 genes regulating axon guidance pathway. (PMID:24321989)
• EN2 levels are increased in affected individuals with an A-C/G-T genotype, supporting EN2 as an autism spectrum disorder susceptibility gene. (PMID:24520327)
• The exact role of EN2 expression in renal carcinoma carcinogenesis requires further investigation. (PMID:24532139)
• En2 identified as a new regulator of T-cell differentiation whose disruption induces a malignant T-cell fate in chronic myelogenous leukemia progression. (PMID:24675889)
• The mean EN2 levels in prostate cancer patients were 3.76-fold higher than those in non-prostate patients after prostate massage. (PMID:25003607)
• Engrailed-2 (EN-2) is a developmentally regulated homeobox gene that is essential for Purkinje cell maturation and normal cerebellar development and patterning. (PMID:25290267)
• EN2 may be a candidate oncogene in bladder cancer by activating the PI3K/Akt pathway and inhibiting PTEN. (PMID:25812440)
• the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells. (PMID:26948025)
• We identified a novel heterozygous missense variant (c.425C>G, p.Pro142Arg) in the Engrailed 2 (EN2) gene in two patients. The G variant has never been reported in public databases and was absent in 100 Thai patients with ASD and 435 Thai controls. A case-control study showed that the G allele of c.425C>G was significantly associated with ASD (PMID:27755371)
• Our data suggest that the functional interaction of miR-33a and EN-2 is involved in tumorigenesis of prostate cancer (PMID:27921232)
• we confirmed that engrailed-2 is the target of hsa-miR-27b in human cytomegalovirus-infected glioma cells (PMID:28343438)
• The critical role of miR212 in inhibiting prostate tumor growth was verified in xenograft models of prostate cancer. These findings highlighted the role of miR212 in PCa progression. More importantly, we speculate that EN-2 is a direct target gene of miR212. (PMID:28713997)
• EN2 is negatively regulated by miR-605, and down-regulation of miR-605 promotes the proliferation and invasion of prostate cancer (PCa) cells by up-regulating EN2, which leads to PCa development and progression (PMID:28943214)
• The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. (PMID:30285763)
• Membrane insertion and secretion of the Engrailed-2 (EN2) transcription factor by prostate cancer cells may induce antiviral activity in the stroma. (PMID:30914795)
• Urine Engrailed-2 (EN2) has no value as prostate cancer prognostic biomarker. (PMID:31692391)
• Bidirectional transfer of homeoprotein EN2 across the plasma membrane requires PIP2. (PMID:32434869)
• Altered staining patterns and expression level of Engrailed-2 in benign prostatic hyperplasia and prostate Cancer predict prostatic disease progression. (PMID:32539763)
• EN2 as an oncogene promotes tumor progression via regulating CCL20 in colorectal cancer. (PMID:32732864)
• Circular RNA circ_0000467 regulates colorectal cancer development via miR-382-5p/EN2 axis. (PMID:33685351)
• Hypermethylation of PDX1, EN2, and MSX1 predicts the prognosis of colorectal cancer. (PMID:35169223)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	en2a	ENSDARG00000026599
danio_rerio	en2b	ENSDARG00000038868
mus_musculus	En2	ENSMUSG00000039095
rattus_norvegicus	En2	ENSRNOG00000006846

Paralogs (3): EN1 (ENSG00000163064), CPHXL (ENSG00000283755), CPHXL2 (ENSG00000284484)

Protein

Protein identifiers

Homeobox protein engrailed-2 — P19622 (reviewed: P19622)

All UniProt accessions (1): P19622

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Disease relevance. Genetic variations in EN2 may be associated with susceptibility to autism.

Similarity. Belongs to the engrailed homeobox family.

RefSeq proteins (1): NP_001418* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000747	HD_engrailed	Domain
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR019549	Homeobox-engrailed_C-terminal	Domain
IPR019737	Homeobox-engrailed_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050720	Engrailed_Homeobox_TFs	Family

Pfam: PF00046, PF10525

UniProt features (10 total): compositionally biased region 4, region of interest 3, chain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19622-F1	62.51	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, AGGAAGC_MIR5163P, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, AAGTCCA_MIR422B_MIR422A, MORF_BRCA1, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, EFC_Q6, BROWNE_HCMV_INFECTION_48HR_DN, CATTTCA_MIR203, KOYAMA_SEMA3B_TARGETS_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), central nervous system neuron differentiation (GO:0021953), neuron differentiation (GO:0030182), midbrain development (GO:0030901), hindbrain development (GO:0030902), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron development (GO:0048666), dopaminergic neuron differentiation (GO:0071542), embryonic brain development (GO:1990403), regulation of DNA-templated transcription (GO:0006355), multicellular organism development (GO:0007275)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), transcription corepressor activity (GO:0003714), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (5): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
neuron differentiation	3
anatomical structure development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
negative regulation of DNA-templated transcription	2
brain development	2
nuclear lumen	2
regulation of DNA-templated transcription	1
central nervous system development	1
cell differentiation	1
generation of neurons	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of DNA-templated transcription	1
cell development	1
embryonic organ development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
multicellular organismal process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription coregulator activity	1
DNA-binding transcription factor binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
nucleolus	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EN2	SLC30A3	Q99726	669
EN2	CNTNAP2	Q9UHC6	623
EN2	FGF8	P55075	589
EN2	WNT1	P04628	584
EN2	PAX2	Q02962	577
EN2	DHH	O43323	572
EN2	ZIC1	Q15915	571
EN2	EGR2	P11161	551
EN2	NEUROG2	Q9H2A3	544
EN2	MDK	P21741	542
EN2	CNPY1	Q3B7I2	531
EN2	SHH	Q15465	526
EN2	ASCL1	P50553	510
EN2	LMBR1	Q8WVP7	502
EN2	QDPR	P09417	492

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NDOR1	CASK	psi-mi:“MI:0914”(association)	0.350
TLE1	TBX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): EN2 (Proximity Label-MS), EN2 (Affinity Capture-RNA), FOXA2 (Reconstituted Complex), EN2 (Affinity Capture-RNA), EN2 (Affinity Capture-MS), EN2 (Affinity Capture-MS), EIF4E (Reconstituted Complex), EN2 (Proximity Label-MS), EN2 (Proximity Label-MS), EN2 (Proximity Label-MS)

ESM2 similar proteins: A0A2Z4LIS9, A6QPM6, A7X8B3, A7X8B5, A7X8B7, A7X8C4, A7X8C7, A7X8C9, A7XW16, A7XW20, A7XW25, O08664, O15054, O43151, O70218, O89113, P09066, P14652, P17542, P19419, P19622, P22091, P23683, P49640, P70061, P78412, P82976, P97503, Q00587, Q04890, Q05916, Q05917, Q12950, Q15270, Q17QW1, Q3U133, Q5JPB2, Q5NCY0, Q6ZW13, Q80WY3

Diamond homologs: A1L2P5, A1YG01, A2D4R4, A2D649, A2T6H5, A2T6Z0, A2T7J2, A3FPJ2, A8DT10, A9L937, B0VXK3, O42365, O42366, O42367, O42368, O42370, O43364, O43365, O43711, O43763, O55144, O93353, O93366, O93367, O93528, P02831, P09022, P09027, P09066, P09638, P0C1T1, P10105, P10181, P14652, P14653, P17487, P17919, P18264, P19622, P20270

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HNuRF	“up-regulates quantity by expression”	EN2
EN2	“down-regulates quantity by repression”	FGF8	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	78
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57200	GRCh38/hg38 7q36.2-36.3(chr7:155007022-159135526)x1	Pathogenic

SpliceAI

246 predictions. Top by Δscore:

Variant	Effect	Δscore
7:155462358:C:A	acceptor_gain	1.0000
7:155462361:A:AG	acceptor_gain	1.0000
7:155462362:T:G	acceptor_gain	1.0000
7:155462365:A:AG	acceptor_gain	1.0000
7:155462366:C:G	acceptor_gain	1.0000
7:155462366:CCCA:C	acceptor_loss	1.0000
7:155462369:A:AG	acceptor_gain	1.0000
7:155462370:G:GG	acceptor_gain	1.0000
7:155462370:G:GT	acceptor_loss	1.0000
7:155459058:TTCAG:T	donor_loss	0.9900
7:155459059:TCAG:T	donor_loss	0.9900
7:155459060:CAG:C	donor_loss	0.9900
7:155459061:AGGT:A	donor_loss	0.9900
7:155459063:G:GC	donor_loss	0.9900
7:155459064:T:G	donor_loss	0.9900
7:155460393:A:G	donor_gain	0.9900
7:155462356:A:AG	acceptor_gain	0.9900
7:155462356:ACC:A	acceptor_gain	0.9900
7:155462369:AG:A	acceptor_gain	0.9900
7:155462370:GG:G	acceptor_gain	0.9900
7:155462370:GGT:G	acceptor_gain	0.9900
7:155462370:GGTC:G	acceptor_gain	0.9900
7:155459657:G:T	donor_gain	0.9700
7:155460371:GGCTT:G	donor_gain	0.9700
7:155460430:G:T	donor_gain	0.9700
7:155458627:G:GT	donor_gain	0.9600
7:155462357:C:G	acceptor_gain	0.9600
7:155462366:CCCAG:C	acceptor_gain	0.9600
7:155462367:CCAGG:C	acceptor_gain	0.9600
7:155462368:CA:C	acceptor_gain	0.9600

AlphaMissense

2127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:155458582:T:C	F69L	1.000
7:155458583:T:C	F69S	1.000
7:155458584:C:A	F69L	1.000
7:155458584:C:G	F69L	1.000
7:155458589:T:A	I71N	1.000
7:155458598:T:A	I74N	1.000
7:155458598:T:C	I74T	1.000
7:155458598:T:G	I74S	1.000
7:155458601:T:C	L75P	1.000
7:155458612:T:C	F79L	1.000
7:155458614:C:A	F79L	1.000
7:155458614:C:G	F79L	1.000
7:155459014:T:A	W213R	1.000
7:155459014:T:C	W213R	1.000
7:155459023:T:A	W216R	1.000
7:155459023:T:C	W216R	1.000
7:155459025:G:C	W216C	1.000
7:155459025:G:T	W216C	1.000
7:155459027:T:A	V217D	1.000
7:155459029:T:G	Y218D	1.000
7:155459032:T:C	C219R	1.000
7:155459033:G:A	C219Y	1.000
7:155459034:T:G	C219W	1.000
7:155459038:C:A	R221S	1.000
7:155459041:T:C	Y222H	1.000
7:155459042:A:G	Y222C	1.000
7:155459047:G:C	D224H	1.000
7:155459048:A:T	D224V	1.000
7:155462377:G:T	R231M	1.000
7:155462418:A:G	K245E	1.000

dbSNP variants (sampled 300 via entrez): RS1000408413 (7:155464196 A>C,G), RS1000431360 (7:155464909 A>C), RS1000865535 (7:155464579 A>G), RS1000929808 (7:155462999 A>G,T), RS1001159337 (7:155458135 A>G,T), RS1001204587 (7:155464310 G>C), RS1001226661 (7:155461510 C>T), RS1001371866 (7:155456204 G>A,C), RS1001434112 (7:155459313 GTCTC>G,GTC,GTCTCTC), RS1003009338 (7:155457030 G>A), RS1003216304 (7:155461170 A>G), RS1003232028 (7:155463710 C>G,T), RS1003310257 (7:155459282 G>A), RS1003431538 (7:155461840 C>T), RS1003515557 (7:155460645 T>C)

Disease associations

OMIM: gene MIM:131310 | disease phenotypes: MIM:611016

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Disputed	AD

Mondo (1): autism, susceptibility to, 10 (MONDO:0012601)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1302	Metabolite levels	1.000000e-06
GCST011743_18	HDL cholesterol levels in HIV infection	5.000000e-06
GCST90006894_1	Cytomegalovirus pp28 antibody levels	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010517	oxalate measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009347	Anti-cytomegalovirus IgG measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lead	affects expression, affects methylation	2
aristolochic acid I	increases expression	1
sodium arsenite	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
PKF115-584	affects expression	1
(+)-JQ1 compound	increases phosphorylation, decreases reaction, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Etoposide	affects response to substance	1
Mitoxantrone	affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Sodium Selenite	increases expression	1

Clinical trials (associated diseases)

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