LRRC8D

Summary

LRRC8D (leucine rich repeat containing 8 VRAC subunit D, HGNC:16992) is a protein-coding gene on chromosome 1p22.2, encoding Volume-regulated anion channel subunit LRRC8D (Q7L1W4). Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes.

Enables volume-sensitive anion channel activity. Involved in several processes, including monoatomic anion transmembrane transport; organic acid transmembrane transport; and protein hexamerization. Located in cytoplasm and plasma membrane. Part of monoatomic ion channel complex.

Source: NCBI Gene 55144 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_001134479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16992
Approved symbol	LRRC8D
Name	leucine rich repeat containing 8 VRAC subunit D
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10470
Ensembl gene	ENSG00000171492
Ensembl biotype	protein_coding
OMIM	612890
Entrez	55144

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 37 protein_coding

ENST00000337338, ENST00000394593, ENST00000414841, ENST00000441269, ENST00000525774, ENST00000527156, ENST00000532201, ENST00000906496, ENST00000906497, ENST00000906498, ENST00000906499, ENST00000906500, ENST00000906501, ENST00000906502, ENST00000906503, ENST00000906504, ENST00000906505, ENST00000906506, ENST00000906507, ENST00000906508, ENST00000906509, ENST00000906510, ENST00000906512, ENST00000906513, ENST00000906514, ENST00000906516, ENST00000906518, ENST00000906519, ENST00000906520, ENST00000906521, ENST00000932575, ENST00000932576, ENST00000932577, ENST00000947385, ENST00000947386, ENST00000947387, ENST00000947388

RefSeq mRNA: 2 — MANE Select: NM_001134479 NM_001134479, NM_018103

CCDS: CCDS726

Canonical transcript exons

ENST00000337338 — 3 exons

Exon	Start	End
ENSE00001211945	89821032	89821291
ENSE00001601130	89933067	89936611
ENSE00003636666	89843638	89843782

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6751 / max 325.6449, expressed in 1815 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3979	15.7869	1700
3987	3.7849	1309
3978	2.3325	1127
3988	0.8485	507
3983	0.3238	143
3982	0.2587	132
3985	0.1041	54
3980	0.0978	26
3984	0.0698	33
3981	0.0478	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	98.06	gold quality
subthalamic nucleus	UBERON:0001906	97.84	gold quality
trigeminal ganglion	UBERON:0001675	97.18	gold quality
lateral globus pallidus	UBERON:0002476	97.06	gold quality
medulla oblongata	UBERON:0001896	97.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.94	gold quality
superior vestibular nucleus	UBERON:0007227	96.81	gold quality
corpus callosum	UBERON:0002336	96.76	gold quality
ventral tegmental area	UBERON:0002691	96.75	gold quality
gingival epithelium	UBERON:0001949	96.51	gold quality
CA1 field of hippocampus	UBERON:0003881	96.37	gold quality
inferior olivary complex	UBERON:0002127	96.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.18	gold quality
dorsal root ganglion	UBERON:0000044	96.08	gold quality
pons	UBERON:0000988	96.06	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.74	gold quality
substantia nigra pars compacta	UBERON:0001965	95.65	gold quality
secondary oocyte	CL:0000655	95.11	gold quality
epithelium of nasopharynx	UBERON:0001951	94.87	gold quality
nasal cavity epithelium	UBERON:0005384	94.81	gold quality
germinal epithelium of ovary	UBERON:0001304	94.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.65	gold quality
olfactory bulb	UBERON:0002264	94.49	gold quality
gingiva	UBERON:0001828	94.48	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.39	gold quality
jejunal mucosa	UBERON:0000399	94.32	gold quality
orbitofrontal cortex	UBERON:0004167	94.15	gold quality
monocyte	CL:0000576	94.11	gold quality
mononuclear cell	CL:0000842	94.10	gold quality
leukocyte	CL:0000738	93.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting LRRC8D, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-3133	99.81	70.92	3506

Literature-anchored findings (GeneRIF, showing 3)

• identified four genes, named TA-LRRP, AD158, LRRC5, and FLJ23420, as unknown LRRC8-like genes (PMID:15094057)
• LRRC8D is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation. (PMID:32415200)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc8db	ENSDARG00000103840
mus_musculus	Lrrc8d	ENSMUSG00000046079
rattus_norvegicus	Lrrc8d	ENSRNOG00000002121

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Volume-regulated anion channel subunit LRRC8D — Q7L1W4 (reviewed: Q7L1W4)

Alternative names: Leucine-rich repeat-containing protein 5, Leucine-rich repeat-containing protein 8D

All UniProt accessions (6): Q7L1W4, E9PJ89, E9PJS7, E9PL08, E9PMF9, Q5VWA0

UniProt curated annotations — full annotation on UniProt →

Function. Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Plays a redundant role in the efflux of amino acids, such as aspartate, in response to osmotic stress. LRRC8A and LRRC8D are required for the uptake of the drug cisplatin. Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition. Also acts as a regulator of glucose-sensing in pancreatic beta cells: VRAC currents, generated in response to hypotonicity- or glucose-induced beta cell swelling, depolarize cells, thereby causing electrical excitation, leading to increase glucose sensitivity and insulin secretion. VRAC channels containing LRRC8D inhibit transport of immunoreactive cyclic dinucleotide GMP-AMP (2’-3’-cGAMP), an immune messenger produced in response to DNA virus in the cytosol. Mediates the import of the antibiotic blasticidin-S into the cell.

Subunit / interactions. Heterohexamer; oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8C and/or LRRC8E) to form a heterohexamer. In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Domain organisation. The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins.

Similarity. Belongs to the LRRC8 family.

RefSeq proteins (2): NP_001127951, NP_060573 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR021040	LRRC8_Pannexin-like	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family

Pfam: PF12534, PF13855

Catalyzed reactions (Rhea), 3 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• iodide(out) = iodide(in) (RHEA:66324)
• taurine(out) = taurine(in) (RHEA:66328)

UniProt features (32 total): repeat 13, topological domain 5, transmembrane region 4, modified residue 3, mutagenesis site 2, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6M04	ELECTRON MICROSCOPY	4.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L1W4-F1	81.50	0.54

Functional residue map

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

Post-translational modifications (3): 241, 242, 246

Disulfide bonds (1): 54–354

Mutagenesis-validated functional residues (2):

Position	Phenotype
44	alters channel anion selectivity.
143	affects ion selectivity of the channel. reduced permeability to negatively charged glutamate and gluconate.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5223345	Miscellaneous transport and binding events
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 232 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, RNGTGGGC_UNKNOWN, TTTGTAG_MIR520D, AREB6_03, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_NUCLEOTIDE_TRANSMEMBRANE_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, AAAGGGA_MIR204_MIR211, GOBP_DICARBOXYLIC_ACID_TRANSPORT

GO Biological Process (8): intracellular glucose homeostasis (GO:0001678), taurine transmembrane transport (GO:0015734), aspartate transmembrane transport (GO:0015810), protein hexamerization (GO:0034214), cellular response to osmotic stress (GO:0071470), monoatomic anion transmembrane transport (GO:0098656), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (2): volume-sensitive anion channel activity (GO:0005225), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nitrogen compound transport	2
cellular anatomical structure	2
glucose homeostasis	1
intracellular chemical homeostasis	1
alkanesulfonate transmembrane transport	1
amino acid transmembrane transport	1
C4-dicarboxylate transport	1
acidic amino acid transport	1
carboxylic acid transmembrane transport	1
protein complex oligomerization	1
response to osmotic stress	1
cellular response to chemical stress	1
cellular response to abiotic stimulus	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic anion channel activity	1
binding	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC8D	PCSK4	Q6UW60	629
LRRC8D	TTYH2	Q9BSA4	575
LRRC8D	BEST1	O76090	552
LRRC8D	CLCN3	P51790	547
LRRC8D	CTSW	P56202	513
LRRC8D	KCP	Q6ZWJ8	510
LRRC8D	TTYH3	Q9C0H2	502
LRRC8D	TTYH1	Q9H313	494
LRRC8D	IHH	Q14623	473
LRRC8D	TNFRSF18	Q9Y5U5	469
LRRC8D	CFTR	P13569	451
LRRC8D	HEPACAM	Q14CZ8	447
LRRC8D	CLCA4	Q14CN2	447
LRRC8D	CLCA2	Q9UQC9	446
LRRC8D	ANO1	Q5XXA6	436

IntAct

31 interactions, top by confidence:

A	B	Type	Score
LRRC8B	SLC25A17	psi-mi:“MI:0914”(association)	0.530
LRRC8D	LRRC8D	psi-mi:“MI:0915”(physical association)	0.490
LRRC8A	LRRC8D	psi-mi:“MI:0915”(physical association)	0.400
SLC17A2	PSMD11	psi-mi:“MI:0914”(association)	0.350
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
SHANK3	ELAVL2	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
NKAIN1	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC17A2	ABCD4	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
NPEPPS	KIF5B	psi-mi:“MI:0914”(association)	0.350
OR2H2	SERPINB8	psi-mi:“MI:0914”(association)	0.350
LRRC8B	CDH2	psi-mi:“MI:0914”(association)	0.350
SLC22A14	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC44A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLC44A5	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
EXOSC4	LRRC8D	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): LRRC8D (Reconstituted Complex), LRRC8D (Affinity Capture-MS), LRRC8D (Affinity Capture-MS), LRRC8D (Affinity Capture-MS), LRRC8D (Affinity Capture-RNA), LRRC8D (Affinity Capture-RNA), LRRC8D (Affinity Capture-MS), LRRC8D (Proximity Label-MS), LRRC8D (Proximity Label-MS), LRRC8D (Affinity Capture-MS), LRRC8D (Affinity Capture-MS), LRRC8D (Proximity Label-MS), LRRC8D (Proximity Label-MS), LRRC8D (Proximity Label-MS), LRRC8D (Proximity Label-MS)

ESM2 similar proteins: A0JPH4, A2AHL1, A8DZH4, D3ZWZ9, E7FFT2, F1QFU0, F1QZE9, P48763, P50482, P86044, Q28CV2, Q32NZ6, Q3TPR7, Q3ZAS0, Q4R7U0, Q4V8U5, Q5F3F5, Q5M7W4, Q5RH73, Q5YCC5, Q5ZKN3, Q68DH5, Q6GQE1, Q6P4P2, Q6UXY8, Q7L1W4, Q7Z2W7, Q7Z402, Q7ZYA0, Q810F5, Q8BH79, Q8C428, Q8C561, Q8CB19, Q8IZK6, Q8N3S3, Q8R455, Q8R4D5, Q8R4P4, Q8R4P5

Diamond homologs: A5PK13, Q3KRC6, Q498T9, Q4V8I7, Q5DU41, Q5U308, Q66JT1, Q68F79, Q6NSJ5, Q6NU09, Q6P9F7, Q7L1W4, Q80WG5, Q8BGR2, Q8IWT6, Q8R502, Q8TDW0, A6NIV6, Q9Z1S7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1483 predictions. Top by Δscore:

Variant	Effect	Δscore
1:89933066:GGAAT:G	acceptor_gain	1.0000
1:89846515:A:AG	acceptor_gain	0.9900
1:89846516:G:GG	acceptor_gain	0.9900
1:89933061:TTCTA:T	acceptor_loss	0.9900
1:89933062:TCTA:T	acceptor_loss	0.9900
1:89933062:TCTAG:T	acceptor_loss	0.9900
1:89933063:CTAG:C	acceptor_loss	0.9900
1:89933063:CTAGG:C	acceptor_loss	0.9900
1:89933064:TA:T	acceptor_loss	0.9900
1:89933064:TAGG:T	acceptor_loss	0.9900
1:89933065:A:AG	acceptor_gain	0.9900
1:89933065:AG:A	acceptor_gain	0.9900
1:89933065:AGG:A	acceptor_loss	0.9900
1:89933065:AGGA:A	acceptor_loss	0.9900
1:89933066:G:A	acceptor_loss	0.9900
1:89933066:G:C	acceptor_loss	0.9900
1:89933066:G:GG	acceptor_gain	0.9900
1:89933066:GG:G	acceptor_gain	0.9900
1:89933066:GGA:G	acceptor_gain	0.9900
1:89846515:AGTCT:A	acceptor_gain	0.9800
1:89846516:GTCTG:G	acceptor_gain	0.9800
1:89895391:C:G	donor_gain	0.9800
1:89933066:GGAA:G	acceptor_gain	0.9800
1:89821288:CAAG:C	donor_loss	0.9700
1:89821289:AAG:A	donor_loss	0.9700
1:89821290:AG:A	donor_loss	0.9700
1:89821291:GG:G	donor_loss	0.9700
1:89821292:G:GC	donor_loss	0.9700
1:89821293:T:G	donor_loss	0.9700
1:89846516:GTCT:G	acceptor_gain	0.9700

AlphaMissense

5730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:89933138:T:A	W24R	1.000
1:89933138:T:C	W24R	1.000
1:89933228:T:C	C54R	1.000
1:89933230:T:G	C54W	1.000
1:89933527:T:G	C153W	1.000
1:89933690:T:A	W208R	1.000
1:89933690:T:C	W208R	1.000
1:89933692:G:C	W208C	1.000
1:89933692:G:T	W208C	1.000
1:89934128:T:A	C354S	1.000
1:89934128:T:C	C354R	1.000
1:89934129:G:C	C354S	1.000
1:89934130:C:G	C354W	1.000
1:89934377:T:C	F437L	1.000
1:89934379:C:A	F437L	1.000
1:89934379:C:G	F437L	1.000
1:89934405:T:C	L446P	1.000
1:89934731:T:A	W555R	1.000
1:89934731:T:C	W555R	1.000
1:89933140:G:C	W24C	0.999
1:89933140:G:T	W24C	0.999
1:89933228:T:A	C54S	0.999
1:89933229:G:A	C54Y	0.999
1:89933229:G:C	C54S	0.999
1:89933525:T:A	C153S	0.999
1:89933525:T:C	C153R	0.999
1:89933526:G:A	C153Y	0.999
1:89933526:G:C	C153S	0.999
1:89933526:G:T	C153F	0.999
1:89933615:T:A	W183R	0.999

dbSNP variants (sampled 300 via entrez): RS1000025483 (1:89821379 C>G), RS1000037636 (1:89864004 A>G), RS1000053139 (1:89877600 G>A), RS1000056223 (1:89906691 A>G), RS1000056682 (1:89821482 T>G), RS1000061123 (1:89841439 C>T), RS1000140670 (1:89890333 C>G), RS1000142680 (1:89928394 A>G), RS1000151720 (1:89855914 A>C), RS1000167531 (1:89846051 T>G), RS1000274733 (1:89921695 C>T), RS1000309603 (1:89883452 T>C), RS1000319902 (1:89840153 G>A), RS1000409975 (1:89846631 T>G), RS1000427376 (1:89919497 A>G)

Disease associations

OMIM: gene MIM:612890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002774_1	Cognitive function	3.000000e-06
GCST003434_11	Obsessive-compulsive symptoms	8.000000e-06
GCST004748_70	Lung cancer	4.000000e-06
GCST004750_98	Squamous cell lung carcinoma	1.000000e-06
GCST006210_1	Thiopurine-induced digestive symptoms in inflammatory bowel disease	7.000000e-07
GCST90002395_312	Mean platelet volume	6.000000e-12
GCST90002395_313	Mean platelet volume	4.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0007802	obsessive-compulsive symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Estradiol	decreases expression, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
resorcinol	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
monomethylarsonous acid	decreases expression	1
abrine	decreases expression	1
prothioconazole	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	decreases methylation	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SV96	HAP1 LRRC8D (-) 1	Cancer cell line	Male
CVCL_SV97	HAP1 LRRC8D (-) 2	Cancer cell line	Male
CVCL_SV98	HAP1 LRRC8D (-) 3	Cancer cell line	Male
CVCL_SV99	HAP1 LRRC8D (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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