ACP6

Summary

ACP6 (acid phosphatase 6, lysophosphatidic, HGNC:29609) is a protein-coding gene on chromosome 1q21.2, encoding Lysophosphatidic acid phosphatase type 6 (Q9NPH0). Hydrolyzes lysophosphatidic acid (LPA) containing a medium length fatty acid chain to the corresponding monoacylglycerol.

This gene encodes a member of the histidine acid phosphatase protein family. The encoded protein hydrolyzes lysophosphatidic acid, which is involved in G protein-coupled receptor signaling, lipid raft modulation, and in balancing lipid composition within the cell. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51205 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 343 total — 204 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_016361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29609
Approved symbol	ACP6
Name	acid phosphatase 6, lysophosphatidic
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	LPAP, ACPL1
Ensembl gene	ENSG00000162836
Ensembl biotype	protein_coding
OMIM	611471
Entrez	51205

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000392988, ENST00000460583, ENST00000487562, ENST00000493129, ENST00000583509, ENST00000609196, ENST00000611629, ENST00000613673, ENST00000614551, ENST00000620634, ENST00000856435, ENST00000856436, ENST00000856437, ENST00000938746, ENST00000954555

RefSeq mRNA: 2 — MANE Select: NM_016361 NM_001323625, NM_016361

CCDS: CCDS928

Canonical transcript exons

ENST00000583509 — 10 exons

Exon	Start	End
ENSE00002685668	147652449	147652549
ENSE00002693185	147650143	147650238
ENSE00002706602	147654194	147654326
ENSE00002716376	147655161	147655248
ENSE00002725866	147669830	147670524
ENSE00003502061	147648246	147648411
ENSE00003724931	147658960	147659039
ENSE00003727583	147659396	147659526
ENSE00003733140	147642230	147647566
ENSE00003750251	147659647	147659775

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 92.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8477 / max 108.5483, expressed in 1593 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14222	3.8644	1443
14223	3.6962	1031
14224	1.2870	793

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.80	gold quality
pancreatic ductal cell	CL:0002079	89.28	silver quality
mucosa of stomach	UBERON:0001199	89.08	gold quality
right adrenal gland	UBERON:0001233	88.11	gold quality
left lobe of thyroid gland	UBERON:0001120	88.07	gold quality
right lobe of thyroid gland	UBERON:0001119	88.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.84	gold quality
right adrenal gland cortex	UBERON:0035827	87.84	gold quality
thyroid gland	UBERON:0002046	87.62	gold quality
metanephros cortex	UBERON:0010533	87.43	gold quality
adenohypophysis	UBERON:0002196	87.25	gold quality
pituitary gland	UBERON:0000007	86.93	gold quality
tibial artery	UBERON:0007610	86.93	gold quality
popliteal artery	UBERON:0002250	86.92	gold quality
corpus epididymis	UBERON:0004359	86.80	gold quality
left adrenal gland	UBERON:0001234	86.76	gold quality
left adrenal gland cortex	UBERON:0035825	86.59	gold quality
islet of Langerhans	UBERON:0000006	86.48	gold quality
endothelial cell	CL:0000115	86.30	gold quality
right lobe of liver	UBERON:0001114	86.23	gold quality
aorta	UBERON:0000947	85.87	gold quality
adrenal gland	UBERON:0002369	85.74	gold quality
mucosa of transverse colon	UBERON:0004991	85.71	gold quality
adrenal cortex	UBERON:0001235	85.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.58	gold quality
lower esophagus	UBERON:0013473	85.57	gold quality
body of stomach	UBERON:0001161	85.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.23	gold quality
apex of heart	UBERON:0002098	85.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.09

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• acid phosphatase-like protein 1 from human intestinal tissue could be associated with interstitial cells of Cajal function ACPL1 (PMID:12010880)
• Human seminal plasma contains this enzyme which converts lysophospholipids to lysophosphatidic acid. (PMID:15280042)
• structures and biochemical studies of human lysophosphatidic acid phosphatase type 6 (PMID:23807634)
• Mutant p53 regulates LPA signaling through lysophosphatidic acid phosphatase type 6. (PMID:30914657)
• The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma. (PMID:36456931)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	acp6	ENSDARG00000040064
mus_musculus	Acp6	ENSMUSG00000028093
rattus_norvegicus	Acp6	ENSRNOG00000017494
drosophila_melanogaster	CG9449	FBGN0036875
drosophila_melanogaster	CG9451	FBGN0036876
drosophila_melanogaster	CG9452	FBGN0036877
caenorhabditis_elegans		WBGENE00007328
caenorhabditis_elegans		WBGENE00007331
caenorhabditis_elegans		WBGENE00008801
caenorhabditis_elegans		WBGENE00008802
caenorhabditis_elegans		WBGENE00008804
caenorhabditis_elegans		WBGENE00009146
caenorhabditis_elegans		WBGENE00015161
caenorhabditis_elegans		WBGENE00016152
caenorhabditis_elegans		WBGENE00022770
caenorhabditis_elegans		WBGENE00206373

Paralogs (5): ACP3 (ENSG00000014257), ACP2 (ENSG00000134575), ACP4 (ENSG00000142513), FRA10AC1 (ENSG00000148690), PXYLP1 (ENSG00000155893)

Protein

Protein identifiers

Lysophosphatidic acid phosphatase type 6 — Q9NPH0 (reviewed: Q9NPH0)

Alternative names: Acid phosphatase 6, lysophosphatidic, Acid phosphatase-like protein 1, PACPL1

All UniProt accessions (7): A0A087WW36, A0A087WWB7, A0A087WYU6, A0A0A0MS36, Q9NPH0, V9GZ71, X5D319

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes lysophosphatidic acid (LPA) containing a medium length fatty acid chain to the corresponding monoacylglycerol. Has highest activity with lysophosphatidic acid containing myristate (C14:0), monounsaturated oleate (C18:1) or palmitate (C16:0), and lower activity with C18:0 and C6:0 lysophosphatidic acid.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

Tissue specificity. Highly expressed in kidney, heart, small intestine, muscle, liver, prostate, testis, ovary and weakly expressed in thymus and colon.

Induction. Induced with the differentiation from myoblast to myotube.

Similarity. Belongs to the histidine acid phosphatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPH0-1	1	yes
Q9NPH0-2	2

RefSeq proteins (2): NP_001310554, NP_057445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000560	His_Pase_clade-2	Family
IPR029033	His_PPase_superfam	Homologous_superfamily
IPR033379	Acid_Pase_AS	Active_site
IPR050645	Histidine_acid_phosphatase	Family

Pfam: PF00328

Enzyme classification (BRENDA):

• EC 3.1.3.106 — 2-lysophosphatidate phosphatase (BRENDA: 7 organisms, 32 substrates, 22 inhibitors, 13 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-ARACHIDONOYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.0059–0.013	2
1-OLEOYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.0062–0.0069	2
1-MYRISTOYL-SN-GLYCEROL 3-PHOSPHATE	0.0051	1
1-OLEOYL-SN-GLYCEROL 3-PHOSPHATE	0.038	1
1-PALMITOYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.003	1
1-STEAROYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.0064	1
1-STEARYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.0042	1
OLEOYL-SN-GLYCEROL 3-PHOSPHATE	0.0286	1
OLEOYL-SN-GLYCEROL-3-PHOSPHATE	0.034	1
PALMITOYL-SN-GLYCEROL 3-PHOSPHATE	0.0479	1
STEAROYL-SN-GLYCEROL 3-PHOSPHATE	0.0393	1

Catalyzed reactions (Rhea), 2 shown:

• a phosphate monoester + H2O = an alcohol + phosphate (RHEA:15017)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphate (RHEA:39835)

UniProt features (58 total): helix 16, strand 13, mutagenesis site 12, turn 8, active site 2, splice variant 2, transit peptide 1, chain 1, region of interest 1, sequence conflict 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4JOB	X-RAY DIFFRACTION	2.17
4JOC	X-RAY DIFFRACTION	2.21
4JOD	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPH0-F1	91.22	0.85

Functional residue map

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

Catalytic / active sites (2): 59 (nucleophile); 335 (proton donor)

Mutagenesis-validated functional residues (12):

Position	Phenotype
62	abolishes enzyme activity.
106	decreases enzyme activity.
110	decreases enzyme activity.
168	abolishes enzyme activity.
257	decreases enzyme activity by interfering with water access to the active site cavity.
257	abolishes enzyme activity by interfering with water access to the active site cavity.
285	decreases activity toward substrates with medium and long aliphatic chains, but not toward substrates with short aliphat
289	decreases activity toward substrates with medium and long aliphatic chains, but not toward substrates with short aliphat
334	abolishes enzyme activity.
335	abolishes enzyme activity.
58	abolishes enzyme activity.
59	abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA

MSigDB gene sets: 166 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, RRAGTTGT_UNKNOWN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, NKX25_02, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GGAMTNNNNNTCCY_UNKNOWN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, AACWWCAANK_UNKNOWN, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, OCT1_03, HFH8_01, FOXJ2_01

GO Biological Process (5): hematopoietic progenitor cell differentiation (GO:0002244), phospholipid metabolic process (GO:0006644), phosphatidic acid biosynthetic process (GO:0006654), lysobisphosphatidic acid metabolic process (GO:2001311), lipid metabolic process (GO:0006629)

GO Molecular Function (3): acid phosphatase activity (GO:0003993), lysophosphatidic acid phosphatase activity (GO:0052642), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatase activity	2
hemopoiesis	1
cell differentiation	1
lipid metabolic process	1
organophosphate metabolic process	1
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
glycerophospholipid metabolic process	1
alditol phosphate metabolic process	1
primary metabolic process	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACP6	PRKAB2	O43741	744
ACP6	FMO5	P49326	697
ACP6	NBPF11	Q86T75	696
ACP6	CHD1L	Q86WJ1	686
ACP6	GPHRA	B7ZAQ6	636
ACP6	GJA8	P48165	584
ACP6	BCL9	O00512	575
ACP6	ACP7	Q6ZNF0	529
ACP6	PDIA3	P30101	527
ACP6	GJA5	P36382	513
ACP6	ACP5	P13686	491
ACP6	MRPL28	Q13084	437
ACP6	SLC27A3	Q5K4L6	436
ACP6	ANKRD34A	Q69YU3	427
ACP6	RBM8A	Q9Y5S9	426

IntAct

17 interactions, top by confidence:

A	B	Type	Score
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
ACP6	FAM9B	psi-mi:“MI:0915”(physical association)	0.370
ACP6	NME4	psi-mi:“MI:0914”(association)	0.350
OCIAD1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
ACP6	COQ9	psi-mi:“MI:0914”(association)	0.350
BOLA3	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
rep	CNK3/IPCEF1	psi-mi:“MI:0914”(association)	0.350
SLC25A25	HAX1	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
ILK	ACP6	psi-mi:“MI:0915”(physical association)	0.000
ACP6	SLC35F6	psi-mi:“MI:0915”(physical association)	0.000
ACP6	GNG7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): ACP6 (Affinity Capture-MS), NME4 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), CYCS (Affinity Capture-MS), NRD1 (Affinity Capture-MS), PMPCB (Affinity Capture-MS), PMPCA (Affinity Capture-MS), ACP6 (Affinity Capture-MS), ACP6 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), ILK (Affinity Capture-MS), ACP6 (Affinity Capture-MS), RGS10 (Affinity Capture-MS), RSU1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A6H730, A6H757, B1H1P9, B6EWW8, D2GZV9, E1BPW0, E1C1L6, F8S0Z7, J3SBP3, J3SEZ3, O14638, O35409, O75356, P06802, P07686, P0DQQ4, P11117, P15309, P15396, P20060, P20611, P20646, P22413, P24638, P24822, P49614, P58242, P70627, P97675, Q0P5F0, Q29548, Q3KQG9, Q3MI05, Q3U4B4, Q4R5N9, Q5NVF6, Q5R5M5, Q5R8C0, Q5VXJ0

Diamond homologs: A6H757, Q09448, Q5R8C0, Q8BP40, Q9NPH0, Q09451, Q09549, Q0IHQ9, Q19076, Q54P71, Q54P72, Q66H78, Q8BHA9, Q8TE99, A6H730, P11117, P20646, Q0P5F0, Q5NVF6, Q8CE08, Q9BZG2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	204
Likely pathogenic	35
Uncertain significance	69
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1330159	GRCh37/hg19 1q21.1-21.2(chr1:146022474-147599371)x3	Pathogenic
144158	GRCh38/hg38 1q21.1-21.2(chr1:145232830-148587578)x3	Pathogenic
144308	GRCh38/hg38 1q21.1-21.2(chr1:147035964-148436984)x1	Pathogenic
144475	GRCh38/hg38 1q21.1-21.2(chr1:147035964-148352079)x3	Pathogenic
144623	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148415560)x3	Pathogenic
144787	GRCh38/hg38 1q21.1-21.2(chr1:146354110-148503773)x1	Pathogenic
144815	GRCh38/hg38 1q21.1-21.2(chr1:146964168-148572213)x3	Pathogenic
146019	GRCh38/hg38 1q21.1-21.2(chr1:146355224-148494171)x3	Pathogenic
146027	GRCh38/hg38 1q21.1-21.2(chr1:145338382-148599763)x3	Pathogenic
146383	GRCh38/hg38 1q21.1-21.2(chr1:147029419-148355961)x3	Pathogenic
146443	GRCh37/hg19 1q21.1-21.2(chr1:145425395-148867610)x3	Pathogenic
146685	GRCh37/hg19 1q21.1-21.2(chr1:142618650-148535229)x3	Pathogenic
146808	GRCh38/hg38 1q21.1-21.2(chr1:144572470-149076087)x3	Pathogenic
147551	GRCh38/hg38 1q21.1-21.2(chr1:147335698-147909284)x3	Pathogenic
147710	GRCh38/hg38 1q21.1-21.2(chr1:143515074-149076087)x3	Pathogenic
148452	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148355961)x1	Pathogenic
148485	GRCh38/hg38 1q21.1-21.2(chr1:145215697-149076087)x3	Pathogenic
148526	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148355961)x1	Pathogenic
148573	GRCh38/hg38 1q21.1-21.2(chr1:144572470-149076087)x3	Pathogenic
148696	GRCh38/hg38 1q21.1-21.2(chr1:147002657-148355961)x1	Pathogenic
148824	GRCh38/hg38 1q21.1-21.2(chr1:147029419-148352079)x3	Pathogenic
148884	GRCh38/hg38 1q21.1-21.2(chr1:147071299-148355961)x1	Pathogenic
148993	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148355961)x1	Pathogenic
149419	GRCh38/hg38 1q21.1-21.2(chr1:145232830-148587578)x3	Pathogenic
149420	GRCh38/hg38 1q21.1-21.2(chr1:145215697-149076087)x4	Pathogenic
149649	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148352084)x3	Pathogenic
149746	GRCh38/hg38 1q21.1-21.2(chr1:146354110-148494217)x1	Pathogenic
149912	GRCh38/hg38 1q21.1-21.2(chr1:147156522-148352084)x3	Pathogenic
149965	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148355961)x1	Pathogenic
150482	GRCh38/hg38 1q21.1-21.2(chr1:147036155-147945622)x1	Pathogenic

SpliceAI

1526 predictions. Top by Δscore:

Variant	Effect	Δscore
1:147652648:C:CC	acceptor_gain	1.0000
1:147654189:CTCA:C	donor_loss	1.0000
1:147654190:TCAC:T	donor_loss	1.0000
1:147654191:CAC:C	donor_loss	1.0000
1:147654192:A:AC	donor_gain	1.0000
1:147654192:AC:A	donor_gain	1.0000
1:147654192:ACCT:A	donor_loss	1.0000
1:147654192:ACCTG:A	donor_gain	1.0000
1:147654193:C:CC	donor_gain	1.0000
1:147654193:CC:C	donor_gain	1.0000
1:147654193:CCT:C	donor_gain	1.0000
1:147654193:CCTG:C	donor_gain	1.0000
1:147654193:CCTGC:C	donor_gain	1.0000
1:147654322:GGCCT:G	acceptor_gain	1.0000
1:147654323:GCCT:G	acceptor_gain	1.0000
1:147654324:CCTC:C	acceptor_gain	1.0000
1:147654325:CT:C	acceptor_gain	1.0000
1:147654327:C:CC	acceptor_gain	1.0000
1:147654331:C:CT	acceptor_gain	1.0000
1:147654332:A:T	acceptor_gain	1.0000
1:147659394:A:AC	donor_gain	1.0000
1:147659395:C:CC	donor_gain	1.0000
1:147659402:T:TA	donor_gain	1.0000
1:147659441:T:TA	donor_gain	1.0000
1:147659642:CTCA:C	donor_loss	1.0000
1:147659644:CA:C	donor_loss	1.0000
1:147659645:ACCT:A	donor_loss	1.0000
1:147659646:C:CG	donor_loss	1.0000
1:147663157:A:AC	donor_gain	1.0000
1:147663158:C:CC	donor_gain	1.0000

AlphaMissense

2818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:147659034:C:G	R162P	0.988
1:147669876:C:G	R58P	0.985
1:147659004:G:A	S172F	0.983
1:147659459:A:G	L139P	0.980
1:147669860:A:C	S63R	0.979
1:147669860:A:T	S63R	0.979
1:147669862:T:G	S63R	0.979
1:147659005:A:G	S172P	0.978
1:147659769:A:G	W76R	0.977
1:147659769:A:T	W76R	0.977
1:147659031:G:A	S163F	0.976
1:147659468:C:A	G136V	0.976
1:147648301:A:G	L363P	0.975
1:147648385:T:A	D335V	0.975
1:147669871:C:A	G60W	0.974
1:147659032:A:G	S163P	0.973
1:147648335:A:G	W352R	0.971
1:147648335:A:T	W352R	0.971
1:147650215:C:T	G302D	0.970
1:147659468:C:T	G136E	0.970
1:147648313:A:G	L359P	0.969
1:147658980:A:G	L180P	0.968
1:147659012:A:C	N169K	0.966
1:147659012:A:T	N169K	0.966
1:147669900:A:G	L50S	0.966
1:147648400:A:G	L330P	0.965
1:147659004:G:T	S172Y	0.964
1:147659028:G:A	T164I	0.964
1:147669864:C:G	R62P	0.964
1:147648268:A:T	V374E	0.963

dbSNP variants (sampled 300 via entrez): RS1000033626 (1:147632273 A>C,G), RS1000467002 (1:147659298 C>G,T), RS1000612063 (1:147639086 G>A,C), RS1000667205 (1:147652834 T>C), RS1000735683 (1:147666934 A>G), RS1000778035 (1:147645771 T>C), RS1000861390 (1:147671552 A>C,G), RS1001007888 (1:147631047 T>C), RS1001034244 (1:147630610 C>T), RS1001044842 (1:147638847 T>C), RS1001380607 (1:147639882 A>C), RS1001571320 (1:147666181 A>G), RS1001577632 (1:147632045 A>T), RS1001659318 (1:147672276 C>T), RS1002472388 (1:147659174 C>T)

Disease associations

OMIM: gene MIM:611471 | disease phenotypes: MIM:612475, MIM:116200, MIM:241550, MIM:612474, MIM:181500, MIM:304050

GenCC curated gene-disease

Mondo (10): chromosome 1q21.1 duplication syndrome (MONDO:0012915), cataract 1 multiple types (MONDO:0007285), hypoplastic left heart syndrome 1 (MONDO:0009433), chromosome 1q21.1 deletion syndrome (MONDO:0012914), autism spectrum disorder (MONDO:0005258), optic atrophy (MONDO:0003608), schizophrenia (MONDO:0005090), neurodevelopmental disorder (MONDO:0700092), Mayer-Rokitansky-Kuster-Hauser syndrome (MONDO:0017771), Aicardi syndrome (MONDO:0010568)

Orphanet (9): 1q21.1 microduplication syndrome (Orphanet:250994), Cataract-microcornea syndrome (Orphanet:1377), Hypoplastic left heart syndrome (Orphanet:2248), 1q21.1 microdeletion syndrome (Orphanet:250989), Mayer-Rokitansky-Küster-Hauser syndrome type 1 (Orphanet:247775), Mayer-Rokitansky-Küster-Hauser syndrome (Orphanet:3109), Aicardi syndrome (Orphanet:50), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004358_1	Methotrexate-induced interstitial lung disease in rheumatoid arthritis	2.000000e-07
GCST006585_373	Blood protein levels	2.000000e-312

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D058540	Aicardi Syndrome	C10.500.034.687; C11.270.019; C16.131.162; C16.131.666.034.687; C16.320.290.019; C16.320.322.030
D065886	Neurodevelopmental Disorders	F03.625
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
C566158	Cataract, Zonular Pulverulent 1 (supp.)
C567291	Chromosome 1q21.1 Deletion Syndrome, 1.35-Mb (supp.)
C567290	Chromosome 1q21.1 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
Lipopolysaccharides	affects cotreatment, increases expression, decreases expression, affects response to substance	2
Nickel	decreases expression	2
Valproic Acid	increases expression, increases methylation	2
beta-lapachone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases 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