MICAL3

Summary

MICAL3 (microtubule associated monooxygenase, calponin and LIM domain containing 3, HGNC:24694) is a protein-coding gene on chromosome 22q11.21, encoding [F-actin]-monooxygenase MICAL3 (Q7RTP6). Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization.

Enables actin binding activity and molecular adaptor activity. Involved in actin filament depolymerization. Located in several cellular components, including Flemming body; intercellular bridge; and nucleoplasm.

Source: NCBI Gene 57553 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 399 total
• MANE Select transcript: NM_015241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24694
Approved symbol	MICAL3
Name	microtubule associated monooxygenase, calponin and LIM domain containing 3
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0819
Ensembl gene	ENSG00000243156
Ensembl biotype	protein_coding
OMIM	608882
Entrez	57553

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000252134, ENST00000383094, ENST00000400561, ENST00000414725, ENST00000424046, ENST00000441493, ENST00000461307, ENST00000462645, ENST00000465886, ENST00000495076, ENST00000498345, ENST00000498573, ENST00000577821, ENST00000578905, ENST00000578984, ENST00000579997, ENST00000580469, ENST00000584751, ENST00000585038, ENST00000672019

RefSeq mRNA: 3 — MANE Select: NM_015241 NM_001122731, NM_001136004, NM_015241

CCDS: CCDS46659, CCDS46660, CCDS46661

Canonical transcript exons

ENST00000441493 — 32 exons

Exon	Start	End
ENSE00000650386	17816690	17816784
ENSE00000650388	17817311	17819129
ENSE00000650390	17821427	17821509
ENSE00000650392	17822030	17822170
ENSE00000650394	17822947	17823060
ENSE00000879027	17827644	17827781
ENSE00001558014	17831854	17832107
ENSE00002688992	17900842	17900997
ENSE00002693380	17902631	17902747
ENSE00002698801	17904632	17904839
ENSE00002704788	17906549	17906886
ENSE00002707115	17899448	17899548
ENSE00002707212	17787649	17790916
ENSE00002708003	17841822	17842017
ENSE00002719648	18024281	18024561
ENSE00002726542	17901878	17901979
ENSE00003461380	17889034	17889230
ENSE00003480785	17896724	17896981
ENSE00003482929	17885878	17886051
ENSE00003493513	17887170	17887232
ENSE00003527655	17808844	17808937
ENSE00003529728	17790998	17791071
ENSE00003545912	17871837	17872023
ENSE00003580828	17893808	17893904
ENSE00003592365	17864899	17864986
ENSE00003601483	17810703	17810813
ENSE00003607110	17865924	17866012
ENSE00003609414	17891485	17891632
ENSE00003612983	17791202	17791301
ENSE00003634930	17887323	17887435
ENSE00003653418	17896246	17896361
ENSE00003676893	17895284	17895410

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9197 / max 369.8003, expressed in 1772 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193113	15.9020	1761
193116	2.9694	876
193112	2.6313	1290
193114	0.2195	84
209380	0.0968	40
193098	0.0929	12
193099	0.0079	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.77	gold quality
right uterine tube	UBERON:0001302	97.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.34	gold quality
cerebellar hemisphere	UBERON:0002245	97.11	gold quality
cerebellar cortex	UBERON:0002129	96.97	gold quality
apex of heart	UBERON:0002098	95.95	gold quality
cerebellum	UBERON:0002037	95.33	gold quality
body of uterus	UBERON:0009853	95.19	gold quality
smooth muscle tissue	UBERON:0001135	94.67	gold quality
colonic epithelium	UBERON:0000397	94.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.51	gold quality
left uterine tube	UBERON:0001303	94.03	gold quality
left testis	UBERON:0004533	94.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.90	gold quality
lower esophagus	UBERON:0013473	93.85	gold quality
right testis	UBERON:0004534	93.82	gold quality
right atrium auricular region	UBERON:0006631	93.61	gold quality
tibial nerve	UBERON:0001323	93.43	gold quality
heart left ventricle	UBERON:0002084	93.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.33	gold quality
muscle of leg	UBERON:0001383	93.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.21	gold quality
gastrocnemius	UBERON:0001388	93.19	gold quality
popliteal artery	UBERON:0002250	92.91	gold quality
tibial artery	UBERON:0007610	92.89	gold quality
right coronary artery	UBERON:0001625	92.74	gold quality
cardiac atrium	UBERON:0002081	92.48	gold quality
cardiac ventricle	UBERON:0002082	92.42	gold quality
mucosa of stomach	UBERON:0001199	92.28	gold quality
right frontal lobe	UBERON:0002810	92.20	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.41
E-GEOD-111727	no	4849.00
E-CURD-135	no	899.10
E-MTAB-11268	no	765.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

5 targeting MICAL3, 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-4282	99.99	75.36	6408
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 6)

• The monooxygenase activity of MICAL3 is required to regulate its own turnover and the concomitant remodeling of vesicle-docking protein complexes. (PMID:21596566)
• data do not support our hypothesis that the association between rs2277831 and primary osteoarthriti is due to the effect this SNP has on MICAL3, BCL2L13 or BID gene expression (PMID:22385522)
• a novel link wherein placenta growth factor-mediated downregulation of paired box protein 5 attenuates miR-648 expression leading to increased endothelin-1 levels that are known to induce Pulmonary hypertension in sickle cell anemia (PMID:25403488)
• Further exploration of the NINL-associated interactome identifies MICAL3, a protein known to interact with Rab8 and to play an important role in vesicle docking and fusion. (PMID:26485645)
• MICAL3 acts as a midbody-associated scaffold for vesicle targeting, which promotes maturation of the intercellular bridge and abscission. (PMID:27528609)
• the niche factor Sema3-stimulated NP1/MICAL3/CRMP2/Numb axis appears to expand Cancer stem-like cells (CSCs) at least partly through increased frequency of MICAL3-mediated symmetric division of CSCs. (PMID:30587593)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mical3a	ENSDARG00000097017
mus_musculus	Mical3	ENSMUSG00000051586
rattus_norvegicus	Mical3	ENSRNOG00000053203

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

[F-actin]-monooxygenase MICAL3 — Q7RTP6 (reviewed: Q7RTP6)

Alternative names: Molecule interacting with CasL protein 3

All UniProt accessions (10): A0A5F9ZHV5, C9J922, E9PP85, Q7RTP6, J3KRP8, J3KSK6, J3KTB6, J3QLA3, J3QQT0, J3QR21

UniProt curated annotations — full annotation on UniProt →

Function. Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission.

Subunit / interactions. Interacts with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B is of low affinity compared to other Rab proteins; at least in case of RAB8A can bind 2 molecules of RAB8A simultaneously through a high and a low affinity binding site, respectively. Interacts with ERC1 and RAB8A; may bridge ERC1 with RAB8A. Interacts with KIF23 and ERC1; enhances the interaction between KIF23 and ERC1. Interacts with NINL isoform 2.

Subcellular location. Cytoplasm. Cell cortex. Cytoskeleton. Nucleus. Midbody. Spindle. Cilium basal body.

Tissue specificity. Ubiquitous.

Domain organisation. The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms).

Similarity. Belongs to the Mical family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q7RTP6-1	1	yes
Q7RTP6-2	2
Q7RTP6-3	3
Q7RTP6-4	4
Q7RTP6-5	5

RefSeq proteins (3): NP_001116203, NP_001129476, NP_056056* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR001781	Znf_LIM	Domain
IPR002938	FAD-bd	Domain
IPR022735	bMERB_dom	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR050540	F-actin_Monoox_Mical	Family
IPR057494	Rossman_Mical	Domain

Pfam: PF00307, PF00412, PF01494, PF12130, PF25413

Catalyzed reactions (Rhea), 1 shown:

• L-methionyl-[F-actin] + NADPH + O2 + H(+) = L-methionyl-(R)-S-oxide-[F-actin] + NADP(+) + H2O (RHEA:51308)

UniProt features (151 total): helix 36, modified residue 24, compositionally biased region 22, strand 19, binding site 14, splice variant 8, turn 7, region of interest 6, sequence conflict 4, domain 3, sequence variant 3, mutagenesis site 2, chain 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6ICI	X-RAY DIFFRACTION	2.3
5SZG	X-RAY DIFFRACTION	2.7
2D88	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTP6-F1	58.99	0.26

Functional residue map

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

Ligand- & substrate-binding residues (14): 97; 116–118; 123–125; 183; 298; 398; 764; 767; 785; 788; 791; 794 …

Post-translational modifications (24): 649, 685, 687, 887, 977, 1134, 1143, 1160, 1192, 1274, 1276, 1278, 1310, 1337, 1341, 1371, 1384, 1433, 1454, 1649 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
93–98	abolishes monooxygenase activity and impairs ability to control docking and fusion of exocytic carriers.
680–683	in mical-3nlsmut; abolishes nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 159 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MORF_ATRX, MODULE_182, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_ACTIN_FILAMENT_ORGANIZATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_SECRETION, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_PROTEIN_DEPOLYMERIZATION, GOMF_ACTIN_BINDING, GOCC_SPINDLE, GOBP_CELL_DIVISION, LIU_SOX4_TARGETS_DN, GOCC_MIDBODY

GO Biological Process (4): exocytosis (GO:0006887), cytoskeleton organization (GO:0007010), actin filament depolymerization (GO:0030042), cell division (GO:0051301)

GO Molecular Function (9): actin binding (GO:0003779), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen (GO:0016709), metal ion binding (GO:0046872), molecular adaptor activity (GO:0060090), FAD binding (GO:0071949), F-actin monooxygenase activity (GO:0120501), monooxygenase activity (GO:0004497), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), spindle (GO:0005819), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), intercellular bridge (GO:0045171), Flemming body (GO:0090543), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), midbody (GO:0030496), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
binding	2
intracellular membraneless organelle	2
cytoplasm	2
cell periphery	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
organelle organization	1
actin polymerization or depolymerization	1
protein depolymerization	1
cellular process	1
cytoskeletal protein binding	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
molecular_function	1
flavin adenine dinucleotide binding	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	1
oxidoreductase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
microtubule cytoskeleton	1
membrane	1
midbody	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MICAL3	RAB8A	P24407	888
MICAL3	NEDD9	Q14511	829
MICAL3	RAB6A	P20340	679
MICAL3	ERC1	Q8IUD2	665
MICAL3	PLXNA4	Q9HCM2	580
MICAL3	RAB1A	P11476	571
MICAL3	RAB1B	Q9H0U4	568
MICAL3	NINL	Q9Y2I6	553
MICAL3	RAB13	P51153	531
MICAL3	TRAPPC2L	Q9UL33	492
MICAL3	ATP9A	O75110	453
MICAL3	SPSB4	Q96A44	441
MICAL3	MICAL1	Q8TDZ2	430
MICAL3	RAB36	O95755	423
MICAL3	MOB4	Q9Y3A3	423
MICAL3	CC2D2A	Q9P2K1	423

IntAct

56 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
RAB8B	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CHCHD4	ENSA	psi-mi:“MI:0914”(association)	0.530
CERKL	PPM1B	psi-mi:“MI:0914”(association)	0.530
MICAL3	KIF23	psi-mi:“MI:0403”(colocalization)	0.490
Mical3	SSB	psi-mi:“MI:0915”(physical association)	0.400
Racgap1		psi-mi:“MI:0915”(physical association)	0.400
Kif23	KIF23	psi-mi:“MI:0915”(physical association)	0.400
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Flot1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Shcbp1	DERL1	psi-mi:“MI:0914”(association)	0.350
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Cd2ap		psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
KIF23	MAP3K4	psi-mi:“MI:0914”(association)	0.350
PICALM	WNK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): MICAL3 (Proximity Label-MS), MICAL3 (Proximity Label-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS), MICAL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094, P05095, P07751, P11277, P11530, P11531, P11532, P11533, P12814, P13395, P13466, P15508, P16086, P16546, P18091, P20111, P21333, P30427, P35609

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	342
Likely benign	20
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

8256 predictions. Top by Δscore:

Variant	Effect	Δscore
22:17790912:GTGAT:G	acceptor_gain	1.0000
22:17790913:TGAT:T	acceptor_gain	1.0000
22:17790914:GAT:G	acceptor_gain	1.0000
22:17790914:GATC:G	acceptor_loss	1.0000
22:17790915:ATCT:A	acceptor_loss	1.0000
22:17790916:TCTT:T	acceptor_loss	1.0000
22:17790917:C:A	acceptor_loss	1.0000
22:17790917:C:CC	acceptor_gain	1.0000
22:17790918:T:C	acceptor_gain	1.0000
22:17790918:T:TC	acceptor_gain	1.0000
22:17790993:CTCA:C	donor_loss	1.0000
22:17790995:CA:C	donor_loss	1.0000
22:17790996:A:AC	donor_gain	1.0000
22:17790996:ACCTT:A	donor_gain	1.0000
22:17790997:C:CC	donor_gain	1.0000
22:17790997:CCTT:C	donor_gain	1.0000
22:17790997:CCTTC:C	donor_gain	1.0000
22:17791068:GGCA:G	acceptor_gain	1.0000
22:17791069:GCA:G	acceptor_gain	1.0000
22:17791070:CA:C	acceptor_gain	1.0000
22:17791070:CAC:C	acceptor_gain	1.0000
22:17791071:AC:A	acceptor_loss	1.0000
22:17791072:C:CC	acceptor_gain	1.0000
22:17791073:T:G	acceptor_loss	1.0000
22:17791081:C:CT	acceptor_gain	1.0000
22:17791082:A:T	acceptor_gain	1.0000
22:17791086:C:CT	acceptor_gain	1.0000
22:17791087:A:T	acceptor_gain	1.0000
22:17791196:ACTCA:A	donor_loss	1.0000
22:17791197:CTCAC:C	donor_loss	1.0000

AlphaMissense

13082 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:17791054:A:G	L1923P	1.000
22:17791060:A:G	L1921P	1.000
22:17791211:A:G	L1914P	1.000
22:17891540:A:G	W547R	1.000
22:17891540:A:T	W547R	1.000
22:17896328:C:G	G414R	1.000
22:17896355:A:G	W405R	1.000
22:17896355:A:T	W405R	1.000
22:17896733:G:C	S399R	1.000
22:17896733:G:T	S399R	1.000
22:17896735:T:G	S399R	1.000
22:17896737:T:A	D398V	1.000
22:17896741:C:A	G397W	1.000
22:17896811:A:C	C373W	1.000
22:17896817:G:C	F371L	1.000
22:17896817:G:T	F371L	1.000
22:17896818:A:G	F371S	1.000
22:17896819:A:G	F371L	1.000
22:17896821:T:A	D370V	1.000
22:17896821:T:C	D370G	1.000
22:17896821:T:G	D370A	1.000
22:17896822:C:G	D370H	1.000
22:17896823:A:C	F369L	1.000
22:17896823:A:T	F369L	1.000
22:17896824:A:G	F369S	1.000
22:17896825:A:G	F369L	1.000
22:17896853:A:C	N359K	1.000
22:17896853:A:T	N359K	1.000
22:17896862:A:C	F356L	1.000
22:17896862:A:T	F356L	1.000

dbSNP variants (sampled 300 via entrez): RS1000010389 (22:17949408 C>T), RS1000022597 (22:17823122 T>G), RS1000031035 (22:17983006 C>A), RS1000069258 (22:17917815 G>A,C), RS1000071686 (22:17975992 T>C), RS1000079811 (22:18000832 G>A), RS1000088769 (22:17986346 C>A,T), RS1000130141 (22:17943967 C>T), RS1000178738 (22:17789562 G>A), RS1000181002 (22:17932080 T>G), RS1000183245 (22:17986660 A>C), RS1000195264 (22:17926971 G>A), RS1000223073 (22:18016353 G>C), RS1000234873 (22:17820516 G>A,C), RS1000247967 (22:17981576 T>G)

Disease associations

OMIM: gene MIM:608882 | disease phenotypes: MIM:614872, MIM:614873

GenCC curated gene-disease

Mondo (2): peroxisome biogenesis disorder 7A (Zellweger) (MONDO:0013938), peroxisome biogenesis disorder 7B (MONDO:0013939)

Orphanet (2): Neonatal adrenoleukodystrophy (Orphanet:44), Zellweger syndrome (Orphanet:912)

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001277_26	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-16
GCST001872_4	Presence of antiphospholipid antibodies	2.000000e-06
GCST002875_64	Diisocyanate-induced asthma	1.000000e-06
GCST004183_14	Lung function (FEV1)	8.000000e-13
GCST005173_8	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	3.000000e-06
GCST005174_52	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	7.000000e-06
GCST005434_29	Pancreatic cancer	8.000000e-07
GCST005606_1	Response to hepatitis B vaccine	9.000000e-06
GCST007094_125	Diastolic blood pressure	4.000000e-08
GCST007429_86	Lung function (FVC)	3.000000e-13
GCST007430_10	Peak expiratory flow	2.000000e-09
GCST007431_77	Lung function (FEV1/FVC)	1.000000e-15
GCST007432_204	FEV1	9.000000e-27
GCST007692_42	Chronic obstructive pulmonary disease	2.000000e-06
GCST007692_7	Chronic obstructive pulmonary disease	4.000000e-10
GCST008158_129	Body mass index	8.000000e-06
GCST008662_11	Lung function in never smokers (low FEV1 vs high FEV1)	2.000000e-07
GCST008664_7	Lung function (low FEV1 vs high FEV1)	2.000000e-09
GCST009363_53	Triglyceride levels x short total sleep time interaction (2df test)	1.000000e-09
GCST011349_30	Gamma glutamyl transferase levels	2.000000e-15
GCST90002388_595	Lymphocyte count	2.000000e-11
GCST90002407_189	White blood cell count	5.000000e-13

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0006995	response to diisocyanate
EFO:0004314	forced expiratory volume
EFO:0004723	coronary artery calcification
EFO:0004645	response to vaccine
EFO:0006336	diastolic blood pressure
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Lead	affects expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation, affects cotreatment	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
pentanal	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Calcitriol	increases expression	1
Cannabidiol	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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