MICAL2

Summary

MICAL2 (microtubule associated monooxygenase, calponin and LIM domain containing 2, HGNC:24693) is a protein-coding gene on chromosome 11p15.3, encoding [F-actin]-monooxygenase MICAL2 (O94851). Methionine monooxygenase that promotes depolymerization of F-actin by mediating oxidation of residues ‘Met-44’ and ‘Met-47’ on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization.

The protein encoded by this gene is a monooxygenase that enhances depolymerization of F-actin and is therefore involved in cytoskeletal dynamics. The encoded protein is a regulator of the SRF signaling pathway. Increased expression of this gene has been associated with cancer progression and metastasis.

Source: NCBI Gene 9645 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 372 total
• MANE Select transcript: NM_001282663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24693
Approved symbol	MICAL2
Name	microtubule associated monooxygenase, calponin and LIM domain containing 2
Location	11p15.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0750, FLJ14966
Ensembl gene	ENSG00000133816
Ensembl biotype	protein_coding
OMIM	608881
Entrez	9645

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 58 protein_coding, 11 protein_coding_CDS_not_defined, 10 retained_intron, 1 nonsense_mediated_decay

ENST00000256194, ENST00000524685, ENST00000524730, ENST00000525075, ENST00000525119, ENST00000525216, ENST00000525444, ENST00000525618, ENST00000525979, ENST00000526065, ENST00000526475, ENST00000526604, ENST00000526672, ENST00000527195, ENST00000527546, ENST00000528931, ENST00000529028, ENST00000529562, ENST00000530021, ENST00000530691, ENST00000530823, ENST00000531732, ENST00000532166, ENST00000532179, ENST00000532420, ENST00000532945, ENST00000533219, ENST00000533389, ENST00000533534, ENST00000534563, ENST00000643523, ENST00000644505, ENST00000645812, ENST00000646065, ENST00000646734, ENST00000675839, ENST00000683283, ENST00000707072, ENST00000864311, ENST00000864312, ENST00000864313, ENST00000864314, ENST00000864315, ENST00000864316, ENST00000864317, ENST00000864318, ENST00000864319, ENST00000864320, ENST00000947337, ENST00000947338, ENST00000947339, ENST00000947340, ENST00000947341, ENST00000947342, ENST00000947343, ENST00000947344, ENST00000947345, ENST00000947346, ENST00000947347, ENST00000947348, ENST00000947349, ENST00000947350, ENST00000947351, ENST00000947352, ENST00000947353, ENST00000947354, ENST00000947355, ENST00000947356, ENST00000947357, ENST00000947358, ENST00000947359, ENST00000947360, ENST00000947361, ENST00000947362, ENST00000947363, ENST00000947364, ENST00000947365, ENST00000947366, ENST00000947367, ENST00000947368

RefSeq mRNA: 16 — MANE Select: NM_001282663 NM_001282663, NM_001282664, NM_001282665, NM_001282666, NM_001282667, NM_001282668, NM_001346292, NM_001346293, NM_001346294, NM_001346295, NM_001346296, NM_001346297, NM_001346298, NM_001346299, NM_001393937, NM_014632

CCDS: CCDS60726, CCDS60727, CCDS7809, CCDS91442, CCDS91443

Canonical transcript exons

ENST00000683283 — 28 exons

Exon	Start	End
ENSE00001100535	12241040	12241162
ENSE00001100588	12242214	12242432
ENSE00001194768	12243987	12244112
ENSE00002140635	12263560	12263785
ENSE00002144280	12138390	12138460
ENSE00003481934	12259795	12259897
ENSE00003504726	12209497	12209598
ENSE00003506435	12262480	12262537
ENSE00003515777	12216219	12216319
ENSE00003526863	12258468	12258556
ENSE00003532412	12242671	12242772
ENSE00003580483	12223411	12223501
ENSE00003581257	12239436	12239585
ENSE00003585145	12255643	12255750
ENSE00003595178	12256785	12256971
ENSE00003607719	12222617	12222743
ENSE00003608543	12226171	12226370
ENSE00003622302	12224673	12224820
ENSE00003634855	12220201	12220458
ENSE00003635173	12208023	12208139
ENSE00003641105	12249184	12249246
ENSE00003645212	12227025	12227131
ENSE00003657253	12204250	12204457
ENSE00003666959	12221644	12221759
ENSE00003679442	12213255	12213410
ENSE00003693474	12236177	12236245
ENSE00003796200	12162079	12162419
ENSE00003916479	12110590	12110726

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.2125 / max 1344.6131, expressed in 1782 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113111	80.8785	1768
113123	0.5631	123
113133	0.3630	149
113132	0.3427	173
113112	0.2556	34
113122	0.2470	112
113135	0.2070	120
113128	0.0952	38
113113	0.0668	32
113126	0.0338	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	99.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.62	gold quality
cerebellar cortex	UBERON:0002129	99.60	gold quality
cerebellum	UBERON:0002037	99.58	gold quality
endothelial cell	CL:0000115	99.31	gold quality
primary visual cortex	UBERON:0002436	99.29	gold quality
paraflocculus	UBERON:0005351	99.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.99	gold quality
descending thoracic aorta	UBERON:0002345	98.94	gold quality
occipital lobe	UBERON:0002021	98.88	gold quality
middle temporal gyrus	UBERON:0002771	98.83	gold quality
blood vessel layer	UBERON:0004797	98.81	gold quality
right coronary artery	UBERON:0001625	98.70	gold quality
saphenous vein	UBERON:0007318	98.69	gold quality
thoracic aorta	UBERON:0001515	98.66	gold quality
ascending aorta	UBERON:0001496	98.62	gold quality
visceral pleura	UBERON:0002401	98.21	gold quality
frontal pole	UBERON:0002795	98.21	gold quality
CA1 field of hippocampus	UBERON:0003881	98.21	gold quality
parietal lobe	UBERON:0001872	98.09	gold quality
aorta	UBERON:0000947	98.03	gold quality
postcentral gyrus	UBERON:0002581	97.96	gold quality
right frontal lobe	UBERON:0002810	97.92	gold quality
prefrontal cortex	UBERON:0000451	97.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.78	gold quality
smooth muscle tissue	UBERON:0001135	97.71	gold quality
colonic mucosa	UBERON:0000317	97.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.58	gold quality
popliteal artery	UBERON:0002250	97.55	gold quality
tibial artery	UBERON:0007610	97.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	119.64
E-ANND-3	yes	14.43
E-CURD-119	yes	11.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting MICAL2, 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-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 13)

• MICAL2-PV is likely to be involved in cancer progression of prostate cancer and could be a candidate as a novel molecular marker and/or target for treatment of prostate cancers. (PMID:16675569)
• although MICAL1 is auto-inhibited by its C-terminal coiled-coil region, MICAL2 remains constitutively active and affects stress fibers, suggesting differential but complementary roles for MICAL1 and MICAL2 in actin microfilament regulation (PMID:22331357)
• These data show that SRF/MRTF-A signaling is regulated by MICAL-2-dependent redox regulation of nuclear actin. (PMID:24440334)
• Data suggest that MICAL2 protein might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy. (PMID:26689989)
• MICAL2 is a major regulator of breast cancer cell migration (PMID:28719045)
• In pulmonary artery hypertension miR-205-5p suppressed pulmonary artery smooth muscle cell proliferation by targeting MICAL2, which activated ERK1/2 signaling. (PMID:30853343)
• MICAL2 expression in endothelial cells participates to inflammation-induced neo-angiogenesis and that MICAL2 inhibition should be tested in cancer- and noncancer-associated neo-angiogenesis, where chronic inflammation represents a relevant pathophysiological mechanism. (PMID:31004710)
• MICAL2 is a novel nucleocytoplasmic shuttling protein promoting cancer invasion and growth of lung adenocarcinoma. (PMID:32360180)
• MICAL2PV suppresses the formation of tunneling nanotubes and modulates mitochondrial trafficking. (PMID:34096155)
• MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-containing Arp2/3 complexes. (PMID:34106209)
• MICAL2 Contributes to Gastric Cancer Cell Proliferation by Promoting YAP Dephosphorylation and Nuclear Translocation. (PMID:34650666)
• MICAL2 contributes to gastric cancer cell migration via Cdc42-dependent activation of E-cadherin/beta-catenin signaling pathway. (PMID:36064550)
• MICAL2 implies immunosuppressive features and acts as an independent and adverse prognostic biomarker in pancreatic cancer. (PMID:38326344)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mical2b	ENSDARG00000020395
danio_rerio	mical2a	ENSDARG00000075608
mus_musculus	Mical2	ENSMUSG00000038244
rattus_norvegicus	Mical2	ENSRNOG00000016210

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), 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), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

[F-actin]-monooxygenase MICAL2 — O94851 (reviewed: O94851)

Alternative names: MICAL C-terminal-like protein, Molecule interacting with CasL protein 2

All UniProt accessions (9): A0A2R8Y771, A0A2R8Y7K9, O94851, E9PJB0, E9PKI3, E9PL42, E9PNC3, E9PRE0, E9PRG5

UniProt curated annotations — full annotation on UniProt →

Function. Methionine monooxygenase that promotes depolymerization of F-actin by mediating oxidation of residues ‘Met-44’ and ‘Met-47’ on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. Regulates the disassembly of branched actin networks also by oxidizing ARP3B-containing ARP2/3 complexes leading to ARP3B dissociation from the network. Acts as a key regulator of the SRF signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A through RhoA.

Subunit / interactions. Interacts with PLXNA4. Interacts with RAB1B. Interacts with MAPK1/ERK2. Interacts with RAB35, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB35 is of low affinity compared to other Rab proteins; at least in case of RAB8A may bind 2 molecules of RAB8A simultaneously through a high and a low affinity binding site, respectively. May interact with MAPK1/ERK2. Interacts with CORO1C; this interaction recruits MICAL2 to the actin filaments.

Subcellular location. Nucleus. Cytoplasm.

Activity regulation. Specifically inhibited by CCG-1423, a small molecule inhibitor of SRF:MKL1/MRTF-A-dependent transcription.

Domain organisation. The C-terminal RAB-binding domain (RBD) (1796-1945), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms).

Similarity. Belongs to the Mical family.

Isoforms (7)

UniProt ID	Names	Canonical?
O94851-7	7	yes
O94851-1	1
O94851-2	2
O94851-3	3
O94851-4	4
O94851-5	5
O94851-6	6

RefSeq proteins (15): NP_001269592, NP_001269593, NP_001269594, NP_001269595, NP_001269596, NP_001333221, NP_001333222, NP_001333223, NP_001333224, NP_001333225, NP_001333226, NP_001333227, NP_001333228, NP_001380866, NP_055447 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR001781	Znf_LIM	Domain
IPR002938	FAD-bd	Domain
IPR016103	ProQ/FinO	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 (90 total): compositionally biased region 14, binding site 14, sequence variant 12, helix 11, region of interest 10, splice variant 9, sequence conflict 7, domain 3, modified residue 2, mutagenesis site 2, strand 2, turn 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5SZH	X-RAY DIFFRACTION	2.3
5SZJ	X-RAY DIFFRACTION	2.66
5SZK	X-RAY DIFFRACTION	2.8
5SZI	X-RAY DIFFRACTION	2.85
2E9K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94851-F1	57.15	0.23

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; 1002; 1005; 1023; 1026; 1029; 1032 …

Post-translational modifications (2): 631, 1688

Mutagenesis-validated functional residues (2):

Position	Phenotype
95	blocks fad binding and abolishes catalytic activity.
677–681	in mical-2nlsmut; abolishes nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 330 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_169, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, VICENT_METASTASIS_UP, AREB6_01, USF_C, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_SPECIFICATION_OF_SYMMETRY, BROWNE_HCMV_INFECTION_48HR_DN

GO Biological Process (6): heart looping (GO:0001947), cytoskeleton organization (GO:0007010), heart development (GO:0007507), sulfur oxidation (GO:0019417), actin filament depolymerization (GO:0030042), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): actin binding (GO:0003779), monooxygenase activity (GO:0004497), NAD(P)H oxidase H2O2-forming activity (GO:0016174), oxidoreductase activity (GO:0016491), 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), mitogen-activated protein kinase binding (GO:0051019), FAD binding (GO:0071949), F-actin monooxygenase activity (GO:0120501), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), actin filament (GO:0005884)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
organelle organization	1
animal organ development	1
circulatory system development	1
sulfur compound metabolic process	1
actin polymerization or depolymerization	1
protein depolymerization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cytoskeletal protein binding	1
oxidoreductase activity	1
oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor	1
catalytic activity	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
protein kinase binding	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
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MICAL2	NEDD9	Q14511	852
MICAL2	PLXNA4	Q9HCM2	713
MICAL2	MAPK1	P28482	584
MICAL2	MSRB1	Q9NZV6	472
MICAL2	MICAL1	Q8TDZ2	455
MICAL2	RHOT2	Q8IXI1	448
MICAL2	UBB	P02248	424
MICAL2	EHBP1L1	Q8N3D4	411
MICAL2	MRTFA	Q969V6	404
MICAL2	KLRK1	P26718	400
MICAL2	RAB8A	P24407	379
MICAL2	MICAL3	Q7RTP6	359
MICAL2	PHACTR1	Q9C0D0	358
MICAL2	VPS13D	Q5THJ4	353
MICAL2	RAB10	P61026	322

IntAct

62 interactions, top by confidence:

A	B	Type	Score
ABCD4	ABCD4	psi-mi:“MI:0914”(association)	0.640
MICAL2	GFAP	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	NOS3	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	PSEN2	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	APP	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	HTT	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	ATXN3	psi-mi:“MI:0915”(physical association)	0.560
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
HLA-DRA	ENTPD6	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530

BioGRID (49): MICAL2 (Affinity Capture-MS), MICAL2 (Affinity Capture-MS), MICAL2 (Affinity Capture-RNA), MICAL2 (Affinity Capture-MS), MICAL2 (Affinity Capture-MS), MICAL2 (Affinity Capture-MS), MICAL2 (Affinity Capture-MS), MICAL2 (Affinity Capture-RNA), FLT1 (Affinity Capture-Western), MICAL2 (Affinity Capture-Western), MICAL2 (Protein-RNA), MICAL2 (Proximity Label-MS), MICAL2 (Proximity Label-MS), MICAL2 (Proximity Label-MS), MICAL2 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8G016, A1A5Q0, B3DH20, D3Z8X7, D4A1F2, E1BTG2, F1MF74, F1RA39, O14730, O60308, O88978, O94851, O95801, P51432, P70566, Q1RMR5, Q1RMT7, Q28FY0, Q2YDM7, Q3UHZ5, Q3UM18, Q4KLT3, Q4R3F0, Q4R8L2, Q5BJT6, Q5EA11, Q5ZJD3, Q6AZN0, Q6P5Q4, Q7Z569, Q80V31, Q863A4, Q863A5, Q863A6, Q863A7, Q86X45, Q8BML1, Q8CCP0, Q8R368, Q8R3H9

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	5	34.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	293
Likely benign	25
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

6510 predictions. Top by Δscore:

Variant	Effect	Δscore
11:12110723:TTCGG:T	donor_loss	1.0000
11:12110724:TCGGT:T	donor_loss	1.0000
11:12110726:GGTAA:G	donor_loss	1.0000
11:12110727:GTAA:G	donor_loss	1.0000
11:12162420:GTA:G	donor_loss	1.0000
11:12162421:T:G	donor_loss	1.0000
11:12204246:GCA:G	acceptor_loss	1.0000
11:12204247:CA:C	acceptor_loss	1.0000
11:12204248:A:AC	acceptor_loss	1.0000
11:12204248:A:AG	acceptor_gain	1.0000
11:12204249:G:GA	acceptor_loss	1.0000
11:12204249:G:GG	acceptor_gain	1.0000
11:12204249:GT:G	acceptor_gain	1.0000
11:12204249:GTGT:G	acceptor_gain	1.0000
11:12204426:G:GT	donor_gain	1.0000
11:12204426:G:T	donor_gain	1.0000
11:12204453:TATCA:T	donor_gain	1.0000
11:12204454:ATCA:A	donor_gain	1.0000
11:12204455:TCA:T	donor_gain	1.0000
11:12204456:CA:C	donor_gain	1.0000
11:12204457:AGTG:A	donor_loss	1.0000
11:12204458:G:GG	donor_gain	1.0000
11:12204458:GTGA:G	donor_loss	1.0000
11:12208018:GACA:G	acceptor_loss	1.0000
11:12208022:G:GT	acceptor_loss	1.0000
11:12208138:AAG:A	donor_loss	1.0000
11:12208139:AGTA:A	donor_loss	1.0000
11:12208140:G:GG	donor_gain	1.0000
11:12208145:G:GG	donor_gain	1.0000
11:12209595:G:GT	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000236 (11:12217952 G>C,T), RS1000047703 (11:12325641 T>G), RS1000060239 (11:12224001 T>C), RS1000066639 (11:12160045 C>T), RS1000070024 (11:12190658 G>C), RS1000088588 (11:12140129 A>T), RS1000089213 (11:12298648 A>G), RS1000090001 (11:12262419 C>T), RS1000108758 (11:12135701 C>T), RS1000120797 (11:12320578 C>T), RS1000130084 (11:12252273 T>A), RS1000130210 (11:12179555 A>G), RS1000131079 (11:12128460 G>A), RS1000138789 (11:12343133 C>A,G,T), RS1000141321 (11:12337787 G>A,C)

Disease associations

OMIM: gene MIM:608881 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001925_1	PR interval	2.000000e-06
GCST002875_36	Diisocyanate-induced asthma	2.000000e-06
GCST002987_10	Stroke	8.000000e-07
GCST003473_10	Aggressiveness in attention deficit hyperactivity disorder	5.000000e-06
GCST003808_1	Non-response to selective serotonin reuptake inhibitors and depression	5.000000e-07
GCST004744_51	Lung adenocarcinoma	3.000000e-06
GCST007649_2	Estimated glomerular filtration rate after 5 years in renal transplantation (recipient effect)	5.000000e-06
GCST010121_10	Ceramide levels (C24:0)	2.000000e-06
GCST010483_1	Cardiovascular death, myocardial infarction or stroke in response to clopidogrel treatment	7.000000e-06
GCST010676_3	Leukoderma in response to rhododendrol	6.000000e-06
GCST012304_4	Major depressive disorder	9.000000e-06
GCST90002385_193	High light scatter reticulocyte count	5.000000e-11
GCST90002386_344	High light scatter reticulocyte percentage of red cells	7.000000e-13
GCST90002387_368	Immature fraction of reticulocytes	3.000000e-09
GCST90002406_362	Reticulocyte fraction of red cells	2.000000e-10
GCST90002407_325	White blood cell count	3.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0006995	response to diisocyanate
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0005199	renal transplant outcome measurement
EFO:0006919	cardiovascular event measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	6
Estradiol	affects cotreatment, increases expression	5
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	increases expression, decreases expression	4
Fulvestrant	affects cotreatment, increases methylation, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	increases expression, increases abundance	2
Doxorubicin	affects expression, affects response to substance	2
Formaldehyde	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
triphenyl phosphate	increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
triadimefon	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1

Clinical trials (associated diseases)

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

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