CRLS1

Summary

CRLS1 (cardiolipin synthase 1, HGNC:16148) is a protein-coding gene on chromosome 20p12.3, encoding Cardiolipin synthase (CMP-forming) (Q9UJA2). Catalyzes the synthesis of cardiolipin (CL) (diphosphatidylglycerol) by specifically transferring a phosphatidyl group from CDP-diacylglycerol to phosphatidylglycerol (PG). It is a selective cancer dependency (DepMap: 60.4% of cell lines).

This gene encodes a member of the CDP-alcohol phosphatidyltransferase class-I family of proteins. The encoded enzyme catalyzes the synthesis of cardiolipin, a phospholipid component of mitochondrial membranes that is critical for mitochondrial function.

Source: NCBI Gene 54675 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation deficiency 57 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 59 total — 3 pathogenic
• Phenotypes (HPO): 37
• Cancer dependency (DepMap): dependent in 60.4% of screened cell lines
• MANE Select transcript: NM_019095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16148
Approved symbol	CRLS1
Name	cardiolipin synthase 1
Location	20p12.3
Locus type	gene with protein product
Status	Approved
Aliases	dJ967N21.6, CLS1, GCD10
Ensembl gene	ENSG00000088766
Ensembl biotype	protein_coding
OMIM	608188
Entrez	54675

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000378863, ENST00000378868, ENST00000452938, ENST00000464921, ENST00000478846, ENST00000489345, ENST00000609154, ENST00000902851, ENST00000902852, ENST00000902853, ENST00000902854, ENST00000902855, ENST00000931460

RefSeq mRNA: 6 — MANE Select: NM_019095 NM_001127458, NM_001323561, NM_001323562, NM_001323563, NM_001323564, NM_019095

CCDS: CCDS13096, CCDS46578

Canonical transcript exons

ENST00000378863 — 7 exons

Exon	Start	End
ENSE00000658307	6009775	6009912
ENSE00001738024	6006123	6006552
ENSE00001908757	6037074	6040053
ENSE00003470377	6031285	6031370
ENSE00003498085	6015361	6015490
ENSE00003532677	6034464	6034555
ENSE00003599603	6032012	6032080

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.4920 / max 685.2201, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183389	32.8159	1821
183388	10.5810	1791
183387	5.0736	1725
183390	0.0215	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.85	gold quality
heart left ventricle	UBERON:0002084	97.12	gold quality
right adrenal gland	UBERON:0001233	97.10	gold quality
left adrenal gland	UBERON:0001234	97.06	gold quality
right adrenal gland cortex	UBERON:0035827	97.06	gold quality
omental fat pad	UBERON:0010414	97.01	gold quality
left adrenal gland cortex	UBERON:0035825	96.97	gold quality
duodenum	UBERON:0002114	96.88	gold quality
liver	UBERON:0002107	96.86	gold quality
apex of heart	UBERON:0002098	96.69	gold quality
right atrium auricular region	UBERON:0006631	96.67	gold quality
heart	UBERON:0000948	96.64	gold quality
body of pancreas	UBERON:0001150	96.52	gold quality
gastrocnemius	UBERON:0001388	96.38	gold quality
fundus of stomach	UBERON:0001160	96.35	gold quality
adipose tissue	UBERON:0001013	96.34	gold quality
body of stomach	UBERON:0001161	96.32	gold quality
adrenal gland	UBERON:0002369	96.15	gold quality
metanephros cortex	UBERON:0010533	96.10	gold quality
cortex of kidney	UBERON:0001225	96.09	gold quality
muscle of leg	UBERON:0001383	95.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.79	gold quality
mucosa of transverse colon	UBERON:0004991	95.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.71	gold quality
stomach	UBERON:0000945	95.60	gold quality
upper lobe of left lung	UBERON:0008952	95.34	gold quality
endometrium	UBERON:0001295	95.33	gold quality
adult mammalian kidney	UBERON:0000082	95.24	gold quality
pancreas	UBERON:0001264	95.20	gold quality
rectum	UBERON:0001052	95.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting CRLS1, 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-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-370-5P	99.78	66.81	706

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• A human candidate gene/cDNA for cardiolipin synthase, C20orf155, was identified. (PMID:16678169)
• hCLS1 protein was localized to the mitochondria when transiently expressed in COS-7 cells (PMID:16716149)
• We describe here a human gene for CLS and its analysis via RNAi knockdown on apoptotic progression. (PMID:16888643)
• anti-cardiolipin antibody positivity is an independent predictor of chronic renal failure (PMID:19048414)
• Patients with solid and non-solid malignancies display anticardiolipin antibodies associated with increased rate of thrombosis (PMID:19048416)
• presence of cardiolipin autoantibodies is criteria for diagnostics of antiphospholipid syndrome (PMID:19052923)
• associated with Libman-Sacks endocarditis, cardiac manifestation of SLE (PMID:19089657)
• antibodies occur frequently in viral infections, particularly, in HIV but not in bacterial infections (PMID:19089659)
• CLS mRNA levels cannot be correlated with CLS enzyme activity nor CL content in the LPS model of inflammation. (PMID:20652826)
• transgenic expression of cardiolipin synthase attenuated maladaptive cardiolipin remodeling and bioenergetic inefficiency in myocardium rendered diabetic by streptozotocin treatment. (PMID:22584571)
• Knockdown of human CRLS1 leads to a cardiolipin decrease, phosphatidylglycerol accumulation and mitochondrial elongation. (PMID:29251771)
• Functionally, LINC00961 overexpression obviously inhibited cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Mechanistically, LINC00961 regulated cardiolipin synthase 1 expression via sponging miR-5581-3p. (PMID:30825207)
• LINC01272 Suppressed Cell Multiplication and Induced Apoptosis Via Regulating MiR-7-5p/CRLS1 Axis in Lung Cancer. (PMID:34099597)
• Deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease. (PMID:35147173)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	crls1	ENSDARG00000038000
mus_musculus	Crls1	ENSMUSG00000027357
rattus_norvegicus	Crls1	ENSRNOG00000021273
drosophila_melanogaster	CLS	FBGN0039360
caenorhabditis_elegans		WBGENE00017763

Paralogs (1): HDHD5 (ENSG00000069998)

Protein

Protein identifiers

Cardiolipin synthase (CMP-forming) — Q9UJA2 (reviewed: Q9UJA2)

Alternative names: Protein GCD10 homolog

All UniProt accessions (2): Q9UJA2, Q6NTG3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of cardiolipin (CL) (diphosphatidylglycerol) by specifically transferring a phosphatidyl group from CDP-diacylglycerol to phosphatidylglycerol (PG). CL is a key phospholipid in mitochondrial membranes and plays important roles in maintaining the functional integrity and dynamics of mitochondria under both optimal and stress conditions.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Highly expressed in tissues such as heart, skeletal muscle and liver.

Disease relevance. Combined oxidative phosphorylation deficiency 57 (COXPD57) [MIM:620167] An autosomal recessive mitochondrial disease characterized by multisystemic features including encephalopathy, neurodevelopmental regression, ocular anomalies, decreased vision, auditory neuropathy, sensorineural hearing loss, and cardiac defects. Disease severity is variable, ranging from premature death in infancy to permanent disability in young adulthood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CDP-alcohol phosphatidyltransferase class-I family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJA2-1	1	yes
Q9UJA2-2	2

RefSeq proteins (6): NP_001120930, NP_001310490, NP_001310491, NP_001310492, NP_001310493, NP_061968* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000462	CDP-OH_P_trans	Family
IPR043130	CDP-OH_PTrfase_TM_dom	Homologous_superfamily
IPR050324	CDP-alcohol_PTase-I	Family

Pfam: PF01066

Enzyme classification (BRENDA):

• EC 2.7.8.41 — cardiolipin synthase (CMP-forming) (BRENDA: 14 organisms, 18 substrates, 4 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
EGG YOLK PHOSPHATIDYLGLYCEROL	0.032–0.0619	3
CDP-1,2-DIMYRISTOYLGLYCEROL	0.0024–0.0029	2
CDP-DIOLEOYLGLYCEROL	0.0014–0.036	2
1,2-DIOLEOYLPHOSPHATIDYLGLYCEROL	1	1
CDP-DIMYRISTOYLGLYCEROL	0.0016	1
DIOLEOYLPHOSPHATIDYLGLYCEROL	0.15	1

Catalyzed reactions (Rhea), 1 shown:

• a CDP-1,2-diacyl-sn-glycerol + a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol) = a cardiolipin + CMP + H(+) (RHEA:32931)

UniProt features (13 total): transmembrane region 5, sequence variant 3, splice variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJA2-F1	69.87	0.35

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1482925	Acyl chain remodelling of PG
R-HSA-1483076	Synthesis of CL

MSigDB gene sets: 222 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, ROZANOV_MMP14_TARGETS_UP, TCF11_01, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (5): cardiolipin biosynthetic process (GO:0032049), phosphatidylglycerol acyl-chain remodeling (GO:0036148), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654), glycerophospholipid biosynthetic process (GO:0046474)

GO Molecular Function (6): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), cardiolipin synthase (CMP-forming) activity (GO:0043337), 2-acylglycerol-3-phosphate O-acyltransferase activity (GO:0047144), CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity (GO:0008444), transferase activity (GO:0016740), phosphotransferase activity, for other substituted phosphate groups (GO:0016780)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lysophosphatidic acid acyltransferase activity	2
phosphatidylglycerol biosynthetic process	1
cardiolipin metabolic process	1
phosphatidylglycerol metabolic process	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
glycerophospholipid metabolic process	1
phospholipid biosynthetic process	1
glycerolipid biosynthetic process	1
acylglycerol O-acyltransferase activity	1
phosphatidyltransferase activity	1
CDP-alcohol phosphatidyltransferase activity	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRLS1	NDUFAF5	Q5TEU4	802
CRLS1	MCM8	Q9UJA3	756
CRLS1	PGS1	Q32NB8	744
CRLS1	TAFAZZIN	Q16635	710
CRLS1	LCLAT1	Q6UWP7	649
CRLS1	PTPMT1	Q8WUK0	632
CRLS1	TAMM41	Q96BW9	628
CRLS1	PURA	Q00577	589
CRLS1	NDUFA11	Q86Y39	589
CRLS1	NDUFS2	O75306	571
CRLS1	NDUFAF3	Q9BU61	549
CRLS1	NDUFA1	O15239	549
CRLS1	NDUFV2	P19404	546
CRLS1	NDUFS3	O75489	542
CRLS1	NDUFS6	O75380	542
CRLS1	NDUFAF2	Q8N183	542

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CRLS1	F2RL1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (9): CRLS1 (Synthetic Lethality), CRLS1 (Two-hybrid), CRLS1 (Negative Genetic), CRLS1 (Negative Genetic), CRLS1 (Biochemical Activity), CRLS1 (Reconstituted Complex), PINK1 (Affinity Capture-Western), CRLS1 (Biochemical Activity), CRLS1 (Reconstituted Complex)

ESM2 similar proteins: A0A2K3D1C8, A0A2K3DU55, A0JMH2, A2YQ58, A8ID74, A8IF44, A8ITV9, A8J1V4, A8JAF2, D0N4E2, E6ZZ11, F5A894, O80952, P22185, Q05B87, Q0C8L9, Q0D3F2, Q0VCH8, Q2QPW2, Q39586, Q3S2U3, Q4VKB4, Q53JI9, Q5GA22, Q5N9A1, Q5U2V5, Q6EU10, Q6PI78, Q6R2V6, Q6Z4A7, Q75BG6, Q75CX4, Q7SEE1, Q80ZM8, Q84V18, Q8GTZ9, Q8GVC7, Q8H8U0, Q8MZC4, Q8RVC7

Diamond homologs: A0A2K3D1C8, A1AC64, O01916, O13899, O80952, P0ABF8, P0ABF9, P0ABG0, P45419, P46322, P63754, P75520, P9WPG4, P9WPG5, Q07560, Q0T3L5, Q0TGS6, Q1RAM8, Q1RKM3, Q322L9, Q32HD9, Q3IYX7, Q3Z2T6, Q4UN77, Q5N9A1, Q5U2V5, Q7VR12, Q80ZM8, Q83R47, Q8D2N9, Q8H8U0, Q8MZC4, Q93YW7, Q9KZP3, Q9M2W3, Q9UJA2, O67908, P36151, P63755, P63756

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
FBXO15	“down-regulates quantity by destabilization”	CRLS1	binding
PINK1	“down-regulates quantity”	CRLS1	phosphorylation
CRLS1	up-regulates	cardiolipin	“chemical modification”
phosphatidylglycerol(1-)	“up-regulates activity”	CRLS1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	39
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2443703	NM_019095.6(CRLS1):c.326T>A (p.Ile109Asn)	Pathogenic
2443704	NM_019095.6(CRLS1):c.515C>A (p.Ala172Asp)	Pathogenic
2443705	NM_019095.6(CRLS1):c.649C>T (p.Leu217Phe)	Pathogenic

SpliceAI

1440 predictions. Top by Δscore:

Variant	Effect	Δscore
20:6009765:T:TA	acceptor_gain	1.0000
20:6009767:T:TA	acceptor_gain	1.0000
20:6009769:TTTCA:T	acceptor_loss	1.0000
20:6009770:TTCAG:T	acceptor_loss	1.0000
20:6009771:TCA:T	acceptor_loss	1.0000
20:6009772:CAGTA:C	acceptor_loss	1.0000
20:6009773:A:AG	acceptor_gain	1.0000
20:6009773:A:AT	acceptor_loss	1.0000
20:6009773:AGTAT:A	acceptor_gain	1.0000
20:6009774:G:GT	acceptor_gain	1.0000
20:6009774:GT:G	acceptor_gain	1.0000
20:6009774:GTA:G	acceptor_gain	1.0000
20:6009774:GTAT:G	acceptor_gain	1.0000
20:6009774:GTATG:G	acceptor_gain	1.0000
20:6009908:ATTTG:A	donor_gain	1.0000
20:6009909:TTTG:T	donor_gain	1.0000
20:6009913:G:GG	donor_gain	1.0000
20:6009914:T:G	donor_loss	1.0000
20:6031371:G:GG	donor_gain	1.0000
20:6031998:T:TA	acceptor_gain	1.0000
20:6031999:G:A	acceptor_gain	1.0000
20:6032006:T:A	acceptor_gain	1.0000
20:6034459:T:G	acceptor_gain	1.0000
20:6034459:TTTA:T	acceptor_loss	1.0000
20:6034461:TA:T	acceptor_loss	1.0000
20:6034462:A:AG	acceptor_gain	1.0000
20:6034462:AGGT:A	acceptor_gain	1.0000
20:6034463:G:GG	acceptor_gain	1.0000
20:6034463:GGT:G	acceptor_gain	1.0000
20:6034463:GGTG:G	acceptor_gain	1.0000

AlphaMissense

1901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:6009908:A:C	D147A	1.000
20:6009908:A:G	D147G	1.000
20:6009909:T:A	D147E	1.000
20:6009909:T:G	D147E	1.000
20:6015368:G:A	G151E	1.000
20:6015433:G:C	D173H	1.000
20:6015434:A:C	D173A	1.000
20:6015434:A:T	D173V	1.000
20:6015435:T:A	D173E	1.000
20:6015435:T:G	D173E	1.000
20:6015448:A:C	S178R	1.000
20:6015450:T:A	S178R	1.000
20:6015450:T:G	S178R	1.000
20:6031315:A:C	D202A	1.000
20:6031315:A:T	D202V	1.000
20:6009801:T:A	N111K	0.999
20:6009801:T:G	N111K	0.999
20:6009818:G:C	R117T	0.999
20:6009896:C:A	A143D	0.999
20:6009905:C:T	T146I	0.999
20:6009907:G:C	D147H	0.999
20:6009908:A:T	D147V	0.999
20:6015364:G:A	D150N	0.999
20:6015364:G:C	D150H	0.999
20:6015365:A:C	D150A	0.999
20:6015365:A:T	D150V	0.999
20:6015366:T:A	D150E	0.999
20:6015366:T:G	D150E	0.999
20:6015367:G:A	G151R	0.999
20:6015367:G:C	G151R	0.999

dbSNP variants (sampled 300 via entrez): RS1000006197 (20:6016375 A>G), RS1000019150 (20:6038600 C>T), RS1000043352 (20:6008764 C>T), RS1000266968 (20:6012922 C>G,T), RS1000352425 (20:6033184 C>T), RS1000408439 (20:6006127 T>C), RS1000536566 (20:6026565 T>C), RS1000597942 (20:6026264 T>A), RS1000740241 (20:6006311 G>A,T), RS1000816260 (20:6019405 G>A), RS1000907292 (20:6020662 G>A,C,T), RS1001022712 (20:6040057 A>G), RS1001045682 (20:6006831 A>G), RS1001076206 (20:6006574 G>A), RS1001088991 (20:6032790 C>G)

Disease associations

OMIM: gene MIM:608188 | disease phenotypes: MIM:620167

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 57	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (1): combined oxidative phosphorylation deficiency 57 (MONDO:0859337)

Orphanet (0):

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000639	Nystagmus
HP:0000710	Hyperorality
HP:0000863	Central diabetes insipidus
HP:0000873	Diabetes insipidus
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001695	Cardiac arrest
HP:0001790	Nonimmune hydrops fetalis
HP:0001955	Unexplained fevers
HP:0002059	Cerebral atrophy
HP:0002104	Apnea
HP:0002376	Developmental regression
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003811	Neonatal death
HP:0005484	Secondary microcephaly
HP:0007110	Central hypoventilation
HP:0007663	Reduced visual acuity
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0009806	Nephrogenic diabetes insipidus
HP:0011504	Bull’s eye maculopathy
HP:0011664	Left ventricular noncompaction cardiomyopathy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009325_65	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	9.000000e-09
GCST009615_19	Triglyceride levels x loop diuretics use interaction	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	decreases methylation	1
Acetaminophen	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Calcitriol	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Colforsin	increases expression	1

Clinical trials (associated diseases)

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