ELP2

Summary

ELP2 (elongator acetyltransferase complex subunit 2, HGNC:18248) is a protein-coding gene on chromosome 18q12.2, encoding Elongator complex protein 2 (Q6IA86). 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: 67.9% of cell lines).

The protein encoded by this gene is a core subunit of the elongator complex, a histone acetyltransferase complex that associates with RNA polymerase II. In addition to histone acetylation, the encoded protein effects transcriptional elongation and may help remodel chromatin.

Source: NCBI Gene 55250 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 58 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 256 total — 7 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 18
• Cancer dependency (DepMap): dependent in 67.9% of screened cell lines
• MANE Select transcript: NM_018255

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18248
Approved symbol	ELP2
Name	elongator acetyltransferase complex subunit 2
Location	18q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10879, StIP
Ensembl gene	ENSG00000134759
Ensembl biotype	protein_coding
OMIM	616054
Entrez	55250

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 50 protein_coding, 8 retained_intron, 7 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay

ENST00000350494, ENST00000351393, ENST00000358232, ENST00000423854, ENST00000442325, ENST00000535093, ENST00000535488, ENST00000536373, ENST00000536830, ENST00000539560, ENST00000540135, ENST00000540323, ENST00000540730, ENST00000540766, ENST00000540799, ENST00000541190, ENST00000541294, ENST00000541748, ENST00000542050, ENST00000542430, ENST00000542824, ENST00000543127, ENST00000543439, ENST00000543861, ENST00000544267, ENST00000544274, ENST00000545302, ENST00000545632, ENST00000867804, ENST00000867805, ENST00000867806, ENST00000867807, ENST00000867808, ENST00000867809, ENST00000867810, ENST00000867811, ENST00000867812, ENST00000867813, ENST00000867814, ENST00000867815, ENST00000867816, ENST00000867817, ENST00000867818, ENST00000867819, ENST00000867820, ENST00000867821, ENST00000867822, ENST00000939562, ENST00000939563, ENST00000939564, ENST00000939565, ENST00000939566, ENST00000939567, ENST00000939568, ENST00000939569, ENST00000939570, ENST00000939571, ENST00000939572, ENST00000939573, ENST00000939574, ENST00000939575, ENST00000939576, ENST00000965727, ENST00000965728, ENST00000965729, ENST00000965730, ENST00000965731, ENST00000965732, ENST00000965733, ENST00000965734, ENST00000965735

RefSeq mRNA: 10 — MANE Select: NM_018255 NM_001242875, NM_001242876, NM_001242877, NM_001242878, NM_001242879, NM_001324465, NM_001324466, NM_001324467, NM_001324468, NM_018255

CCDS: CCDS11918, CCDS56065, CCDS56066, CCDS56067, CCDS56068, CCDS56069

Canonical transcript exons

ENST00000358232 — 22 exons

Exon	Start	End
ENSE00000948446	36146250	36146381
ENSE00001108477	36154850	36154999
ENSE00001888222	36174485	36180557
ENSE00002281020	36129899	36130071
ENSE00003469213	36145948	36146048
ENSE00003469989	36136307	36136377
ENSE00003483794	36159735	36159830
ENSE00003484344	36144939	36145034
ENSE00003486181	36142281	36142347
ENSE00003511221	36158835	36158904
ENSE00003522263	36164475	36164667
ENSE00003547054	36142826	36142966
ENSE00003549652	36156466	36156654
ENSE00003559372	36171047	36171160
ENSE00003566807	36138270	36138426
ENSE00003573174	36159958	36160015
ENSE00003575560	36141137	36141201
ENSE00003622880	36170063	36170196
ENSE00003642433	36138795	36138872
ENSE00003662412	36160932	36161004
ENSE00003675352	36167101	36167222
ENSE00003680049	36133238	36133316

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.9291 / max 531.8351, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169954	65.6132	1822
169952	1.6694	452
169955	0.4966	109
169953	0.1500	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	97.84	gold quality
calcaneal tendon	UBERON:0003701	97.48	gold quality
right ovary	UBERON:0002118	97.31	gold quality
adrenal tissue	UBERON:0018303	97.18	gold quality
skin of abdomen	UBERON:0001416	96.84	gold quality
ovary	UBERON:0000992	96.81	gold quality
skin of leg	UBERON:0001511	96.71	gold quality
ganglionic eminence	UBERON:0004023	96.71	gold quality
colonic epithelium	UBERON:0000397	96.64	gold quality
right uterine tube	UBERON:0001302	96.58	gold quality
body of pancreas	UBERON:0001150	96.56	gold quality
endocervix	UBERON:0000458	96.42	gold quality
right lobe of liver	UBERON:0001114	96.38	gold quality
tibial nerve	UBERON:0001323	96.32	gold quality
mucosa of stomach	UBERON:0001199	96.28	gold quality
stromal cell of endometrium	CL:0002255	96.07	gold quality
adenohypophysis	UBERON:0002196	95.96	gold quality
body of uterus	UBERON:0009853	95.93	gold quality
ventricular zone	UBERON:0003053	95.84	gold quality
tendon	UBERON:0000043	95.80	gold quality
zone of skin	UBERON:0000014	95.46	gold quality
pancreas	UBERON:0001264	95.39	gold quality
pituitary gland	UBERON:0000007	95.37	gold quality
endothelial cell	CL:0000115	95.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.22	gold quality
prostate gland	UBERON:0002367	95.16	gold quality
cortical plate	UBERON:0005343	95.12	gold quality
ectocervix	UBERON:0012249	95.11	gold quality
tendon of biceps brachii	UBERON:0008188	95.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-135	no	531.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 67.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Elp2 and STAT-3 mediate, at least in part, the stimulation of Hsp70 expression by 4PBA. (PMID:22069317)
• Studied the possible relationship between STATIP1, STAT3 and CML resistance. (PMID:25417721)
• ELP2 mutation is implicated in severe intellectual disability, spastic diplegia, and self-injurious behavior described in two brothers. (PMID:25847581)
• Novel Variants of ELP2 and PIAS1 in the Interferon Gamma Signaling Pathway Are Associated with Non-Small Cell Lung Cancer Survival. (PMID:32493705)
• Clinical and molecular findings in a Turkish family with an ultra-rare condition, ELP2-related neurodevelopmental disorder. (PMID:33393008)
• Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype. (PMID:33976153)
• ELP2 compound heterozygous variants associated with cortico-cerebellar atrophy, nodular heterotopia and epilepsy: Phenotype expansion and review of the literature. (PMID:34653680)
• Epilepsy or neurodevelopmental disorders are associated with homozygous and pathogenic ELP2 variation in three siblings. (PMID:36787709)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	elp2	ENSDARG00000017199
mus_musculus	Elp2	ENSMUSG00000024271
rattus_norvegicus	Elp2	ENSRNOG00000015301
drosophila_melanogaster	Elp2	FBGN0033540
caenorhabditis_elegans		WBGENE00013738

Protein

Protein identifiers

Elongator complex protein 2 — Q6IA86 (reviewed: Q6IA86)

Alternative names: SHINC-2, STAT3-interacting protein 1

All UniProt accessions (6): Q6IA86, F5GWY6, F5GX79, F5GYE9, H0YFW0, K7ER35

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. Interacts with STAT3 and JAKs.

Subcellular location. Cytoplasm. Nucleus.

Disease relevance. Intellectual developmental disorder, autosomal recessive 58 (MRT58) [MIM:617270] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT58 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Folds into a two seven-bladed beta-propeller structure which is required for elongator complex assembly.

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

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the WD repeat ELP2 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q6IA86-1	1	yes
Q6IA86-2	2
Q6IA86-3	3
Q6IA86-4	4
Q6IA86-5	5
Q6IA86-6	6
Q6IA86-7	7

RefSeq proteins (10): NP_001229804, NP_001229805, NP_001229806, NP_001229807, NP_001229808, NP_001311394, NP_001311395, NP_001311396, NP_001311397, NP_060725* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR037289	Elp2	Family

Pfam: PF00400

UniProt features (119 total): strand 63, repeat 14, sequence variant 10, turn 9, sequence conflict 9, splice variant 6, mutagenesis site 5, helix 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8PTX	ELECTRON MICROSCOPY	2.87
8PTZ	ELECTRON MICROSCOPY	3.35
8PTY	ELECTRON MICROSCOPY	3.58
8PU0	ELECTRON MICROSCOPY	4.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IA86-F1	89.49	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (5):

Position	Phenotype
1–17	abolishes interaction with elp1 and elp3.
634	no effect on interaction with elp1 or elp3; when associated with a-636, a-670 and a-689.
636	no effect on interaction with elp1 or elp3; when associated with a-634, a-670 and a-689.
670	no effect on interaction with elp1 or elp3; when associated with a-634, a-636 and a-689.
689	no effect on interaction with elp1 or elp3; when associated with a-634, a-636 and a-670.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 155 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GGGTGGRR_PAX4_03, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, chr18q12, GOBP_RNA_MODIFICATION, WANG_LMO4_TARGETS_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, NKX25_01, ELK1_01

GO Biological Process (6): tRNA wobble uridine modification (GO:0002098), regulation of transcription by RNA polymerase II (GO:0006357), transcription elongation by RNA polymerase II (GO:0006368), regulation of translation (GO:0006417), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), tRNA processing (GO:0008033)

GO Molecular Function (3): protein kinase binding (GO:0019901), RNA polymerase II complex binding (GO:0000993), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), 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	3
transcription by RNA polymerase II	2
tRNA wobble base modification	1
regulation of DNA-templated transcription	1
DNA-templated transcription elongation	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via STAT	1
RNA processing	1
tRNA metabolic process	1
kinase binding	1
RNA polymerase core enzyme binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	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

1840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELP2	ELP5	Q8TE02	982
ELP2	ELP3	Q9H9T3	970
ELP2	ELP6	Q0PNE2	911
ELP2	ELP1	O95163	886
ELP2	ELP4	Q96EB1	872
ELP2	CTU1	Q7Z7A3	600
ELP2	ADAT3	Q96EY9	588
ELP2	NR5A1	Q13285	584
ELP2	CTU2	Q2VPK5	550
ELP2	MOCOS	Q96EN8	543
ELP2	ALKBH8	Q96BT7	542
ELP2	NSUN2	Q08J23	541
ELP2	RMP24	Q32NC0	530
ELP2	STAT3	P40763	472
ELP2	URM1	Q9BTM9	468

IntAct

53 interactions, top by confidence:

A	B	Type	Score
ELP3	ELP1	psi-mi:“MI:0914”(association)	0.840
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
ELP2	ELP1	psi-mi:“MI:0914”(association)	0.620
ELP1	ELP2	psi-mi:“MI:0914”(association)	0.620
ELP1	ELP2	psi-mi:“MI:0915”(physical association)	0.620
ELP4	ELP1	psi-mi:“MI:0914”(association)	0.600
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
ELP2	DNAJA2	psi-mi:“MI:0914”(association)	0.530
PLEKHN1	ELP1	psi-mi:“MI:0914”(association)	0.530
CAMK2D	ELP1	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ELP2	COX4I1	psi-mi:“MI:0915”(physical association)	0.400
ELP2	PADI4	psi-mi:“MI:0915”(physical association)	0.400
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
DLD	IRS4	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350
DUSP9	LTN1	psi-mi:“MI:0914”(association)	0.350
CSNK1D	TMEM131L	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
ASAP3	ASAP2	psi-mi:“MI:0914”(association)	0.350
FAM219B	SPAG9	psi-mi:“MI:0914”(association)	0.350
MPG	ELP1	psi-mi:“MI:0914”(association)	0.350
RAB24	UBA1	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): ELP2 (Affinity Capture-RNA), ELP2 (Affinity Capture-RNA), ELP2 (Affinity Capture-RNA), ELP2 (Affinity Capture-MS), ELP2 (Affinity Capture-MS), ELP2 (Affinity Capture-MS), ELP2 (Co-fractionation), ELP2 (Co-fractionation), ELP2 (Co-fractionation), ELP2 (Co-fractionation), IKBKAP (Co-fractionation), ELP2 (Affinity Capture-MS), ELP2 (Affinity Capture-Western), IKBKAP (Affinity Capture-Western), ELP3 (Affinity Capture-Western)

ESM2 similar proteins: A0A2R8QP51, A2RRH5, A5A779, A5PK19, E9PYK3, O35828, P13676, P13798, P19205, P25154, P50747, P79106, P80227, P83006, Q05AM5, Q08602, Q0V8R7, Q0VBY8, Q14CH1, Q3SZD4, Q496Z0, Q498R1, Q499N3, Q4VBE8, Q5EA80, Q5NVK5, Q5PPG7, Q5XIA3, Q64350, Q6IA86, Q86TI2, Q8BNV1, Q8BVG4, Q8BYR1, Q8C1A3, Q8CHW4, Q8N6R0, Q8R146, Q8VDG7, Q91WG4

Diamond homologs: F4I1S7, O94533, P0CS38, P0CS39, P87314, Q05AM5, Q0UNA9, Q2UBU2, Q496Z0, Q4IBR4, Q5EBD9, Q6IA86, Q7K4B3, Q86H45, Q91WG4, B0XAF3, P42935, B0G0Z3, P41318, Q94BR4, Q9AV81, Q9Y6I7, Q6C553, P32479, Q5ACW8, Q6BYU4, Q6CXX3, Q6ZPG2, Q74ZN0, Q03177, A4REK3, Q0UNC6, Q10051, Q9FNN2, A3LTS5, P25635, Q6CU59

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ELP2	“form complex”	“Elongator complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	9
Uncertain significance	160
Likely benign	33
Benign	7

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
2402422	NM_018255.4(ELP2):c.1741_1742del (p.Leu581fs)	Pathogenic
3336513	NM_018255.4(ELP2):c.418C>T (p.Arg140Ter)	Pathogenic
3339533	NM_018255.4(ELP2):c.907C>T (p.Gln303Ter)	Pathogenic
374911	NM_018255.4(ELP2):c.1663A>C (p.Thr555Pro)	Pathogenic
374912	NM_018255.4(ELP2):c.1385G>T (p.Arg462Leu)	Pathogenic
4282463	NM_018255.4(ELP2):c.574C>T (p.Gln192Ter)	Pathogenic
870397	NM_018255.4(ELP2):c.1657C>T (p.Gln553Ter)	Pathogenic
1012184	NM_018255.4(ELP2):c.2460_2461del (p.Arg820fs)	Likely pathogenic
1012185	NM_018255.4(ELP2):c.1214C>T (p.Thr405Ile)	Likely pathogenic
1992333	NM_018255.4(ELP2):c.2084_2087del (p.Val695fs)	Likely pathogenic
2573075	NM_018255.4(ELP2):c.2237del (p.Cys746fs)	Likely pathogenic
3067957	NM_018255.4(ELP2):c.1443_1458dup (p.Cys487fs)	Likely pathogenic
4292434	NM_018255.4(ELP2):c.2065C>T (p.Arg689Ter)	Likely pathogenic
432384	NM_018255.4(ELP2):c.1518_1521del (p.Asn506fs)	Likely pathogenic
4845862	NM_018255.4(ELP2):c.2209C>T (p.Arg737Ter)	Likely pathogenic
624108	NM_018255.4(ELP2):c.1714del (p.Cys572fs)	Likely pathogenic

SpliceAI

3609 predictions. Top by Δscore:

Variant	Effect	Δscore
18:36133235:A:G	acceptor_gain	1.0000
18:36133236:A:AG	acceptor_gain	1.0000
18:36133236:A:AT	acceptor_loss	1.0000
18:36133237:G:GG	acceptor_gain	1.0000
18:36133237:GA:G	acceptor_gain	1.0000
18:36133237:GAAA:G	acceptor_gain	1.0000
18:36133237:GAAAA:G	acceptor_gain	1.0000
18:36133313:GGCT:G	donor_gain	1.0000
18:36133314:GCT:G	donor_gain	1.0000
18:36133314:GCTG:G	donor_gain	1.0000
18:36133317:G:GG	donor_gain	1.0000
18:36136302:TTCA:T	acceptor_loss	1.0000
18:36136304:CA:C	acceptor_loss	1.0000
18:36136305:A:AG	acceptor_gain	1.0000
18:36136306:G:GG	acceptor_gain	1.0000
18:36136306:GC:G	acceptor_gain	1.0000
18:36136306:GCC:G	acceptor_gain	1.0000
18:36136306:GCCC:G	acceptor_gain	1.0000
18:36136374:TCAGG:T	donor_loss	1.0000
18:36136378:G:GA	donor_loss	1.0000
18:36136379:T:G	donor_loss	1.0000
18:36138262:T:A	acceptor_gain	1.0000
18:36138265:TTCA:T	acceptor_loss	1.0000
18:36138268:A:AC	acceptor_loss	1.0000
18:36138268:A:AG	acceptor_gain	1.0000
18:36138269:G:GC	acceptor_gain	1.0000
18:36138269:G:GT	acceptor_loss	1.0000
18:36138269:GC:G	acceptor_gain	1.0000
18:36138269:GCT:G	acceptor_gain	1.0000
18:36138269:GCTT:G	acceptor_gain	1.0000

AlphaMissense

5430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:36164620:G:C	R636P	1.000
18:36142846:A:C	S226R	0.999
18:36142848:C:A	S226R	0.999
18:36142848:C:G	S226R	0.999
18:36146010:T:A	W319R	0.999
18:36146010:T:C	W319R	0.999
18:36154962:G:C	R413T	0.999
18:36156488:G:C	R433T	0.999
18:36156488:G:T	R433M	0.999
18:36156489:G:C	R433S	0.999
18:36156489:G:T	R433S	0.999
18:36156563:A:T	E458V	0.999
18:36156566:A:T	K459I	0.999
18:36158881:T:C	L504S	0.999
18:36159979:T:C	L551P	0.999
18:36159996:T:A	W557R	0.999
18:36159996:T:C	W557R	0.999
18:36160991:C:A	A583D	0.999
18:36164508:T:A	W599R	0.999
18:36164508:T:C	W599R	0.999
18:36164563:T:A	V617D	0.999
18:36164610:T:C	S633P	0.999
18:36164611:C:T	S633F	0.999
18:36164614:G:C	R634T	0.999
18:36164614:G:T	R634I	0.999
18:36164615:A:C	R634S	0.999
18:36164615:A:T	R634S	0.999
18:36164616:G:C	D635H	0.999
18:36164625:T:A	W638R	0.999
18:36164625:T:C	W638R	0.999

dbSNP variants (sampled 300 via entrez): RS1000010237 (18:36157273 G>A), RS1000089263 (18:36148363 C>T), RS1000238147 (18:36150909 T>G), RS1000396882 (18:36166481 C>T), RS1000512309 (18:36152814 C>T), RS1000731839 (18:36179092 A>C,G), RS1000791246 (18:36133979 G>A,T), RS1000792127 (18:36146207 T>C), RS1000817581 (18:36178775 A>G), RS1000863179 (18:36161753 G>A), RS1000920856 (18:36155348 A>G), RS1000974552 (18:36152548 C>A), RS1001098663 (18:36177134 G>T), RS1001144934 (18:36149587 A>G), RS1001172720 (18:36174446 T>C,G)

Disease associations

OMIM: gene MIM:616054 | disease phenotypes: MIM:617270, MIM:616269

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 58	Strong	Autosomal recessive

Mondo (3): intellectual disability, autosomal recessive 58 (MONDO:0014996), progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome (MONDO:0014559), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (1): Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome (Orphanet:457212)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000718	Aggressive behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001266	Choreoathetosis
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0002421	Poor head control
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0004322	Short stature
HP:0008936	Axial hypotonia
HP:0011856	Pica
HP:0100716	Self-injurious behavior

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST012020_159	Serum metabolite levels	9.000000e-11
GCST012021_84	Serum metabolite levels	9.000000e-11

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
hydroquinone	decreases expression	1
beta-methylcholine	affects expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzene	increases expression	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Dichromate	decreases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery