IMMT

Summary

IMMT (inner membrane mitochondrial protein, HGNC:6047) is a protein-coding gene on chromosome 2p11.2, encoding MICOS complex subunit MIC60 (Q16891). Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.

Enables RNA binding activity. Involved in cristae formation. Located in mitochondrial inner membrane. Part of MICOS complex.

Source: NCBI Gene 10989 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 130 total
• Druggable target: yes
• MANE Select transcript: NM_006839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6047
Approved symbol	IMMT
Name	inner membrane mitochondrial protein
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	P87, P89, HMP, MINOS2, Mic60, MICOS60
Ensembl gene	ENSG00000132305
Ensembl biotype	protein_coding
OMIM	600378
Entrez	10989

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 43 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000254636, ENST00000409051, ENST00000409258, ENST00000410111, ENST00000419070, ENST00000442664, ENST00000449247, ENST00000460081, ENST00000474969, ENST00000486633, ENST00000490238, ENST00000910384, ENST00000910385, ENST00000910386, ENST00000910387, ENST00000910388, ENST00000923521, ENST00000923522, ENST00000923523, ENST00000962805, ENST00000962806, ENST00000962807, ENST00000962808, ENST00000962809, ENST00000962810, ENST00000962811, ENST00000962812, ENST00000962813, ENST00000962814, ENST00000962815, ENST00000962816, ENST00000962817, ENST00000962818, ENST00000962819, ENST00000962820, ENST00000962821, ENST00000962822, ENST00000962823, ENST00000962824, ENST00000962825, ENST00000962826, ENST00000962827, ENST00000962828, ENST00000962829, ENST00000962830, ENST00000962831, ENST00000962832, ENST00000962833

RefSeq mRNA: 47 — MANE Select: NM_006839 NM_001100169, NM_001100170, NM_001400086, NM_001400087, NM_001400088, NM_001400089, NM_001400090, NM_001400091, NM_001400100, NM_001400101, NM_001400102, NM_001400103, NM_001400104, NM_001400105, NM_001400106, NM_001400107, NM_001400108, NM_001400109, NM_001400110, NM_001400111, NM_001400112, NM_001400113, NM_001400114, NM_001400115, NM_001400116, NM_001400117, NM_001400118, NM_001400119, NM_001400120, NM_001400121, NM_001400122, NM_001400123, NM_001400124, NM_001400125, NM_001400126, NM_001400127, NM_001400128, NM_001400129, NM_001400130, NM_001400131, NM_001400132, NM_001400133, NM_001400134, NM_001400135, NM_001400137, NM_001400138, NM_006839

CCDS: CCDS46355, CCDS46356, CCDS46357, CCDS92794

Canonical transcript exons

ENST00000410111 — 15 exons

Exon	Start	End
ENSE00000768002	86158592	86158721
ENSE00001579120	86151297	86151520
ENSE00001579210	86195338	86195462
ENSE00001603077	86143936	86144881
ENSE00001678065	86146068	86146197
ENSE00001730137	86147702	86147833
ENSE00002515793	86153560	86153574
ENSE00003502701	86171208	86171345
ENSE00003510496	86159536	86159671
ENSE00003514779	86179433	86179622
ENSE00003602665	86173650	86173761
ENSE00003609200	86166508	86166644
ENSE00003610406	86170749	86170844
ENSE00003620029	86161976	86162079
ENSE00003691137	86181299	86181372

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.5383 / max 286.2854, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29526	77.7681	1826
29527	1.5862	1017
29525	0.1840	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart left ventricle	UBERON:0002084	97.94	gold quality
cardiac ventricle	UBERON:0002082	97.92	gold quality
adrenal tissue	UBERON:0018303	97.89	gold quality
gastrocnemius	UBERON:0001388	97.80	gold quality
apex of heart	UBERON:0002098	97.63	gold quality
right atrium auricular region	UBERON:0006631	97.60	gold quality
biceps brachii	UBERON:0001507	97.55	gold quality
muscle of leg	UBERON:0001383	97.52	gold quality
cardiac atrium	UBERON:0002081	97.44	gold quality
heart right ventricle	UBERON:0002080	97.38	gold quality
heart	UBERON:0000948	97.30	gold quality
muscle organ	UBERON:0001630	97.22	gold quality
skeletal muscle organ	UBERON:0014892	97.22	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.08	gold quality
right adrenal gland cortex	UBERON:0035827	97.06	gold quality
right adrenal gland	UBERON:0001233	97.02	gold quality
body of tongue	UBERON:0011876	96.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.79	gold quality
deltoid	UBERON:0001476	96.77	gold quality
left ventricle myocardium	UBERON:0006566	96.77	gold quality
triceps brachii	UBERON:0001509	96.72	gold quality
left adrenal gland	UBERON:0001234	96.65	gold quality
skeletal muscle tissue	UBERON:0001134	96.63	gold quality
adrenal gland	UBERON:0002369	96.46	gold quality
left adrenal gland cortex	UBERON:0035825	96.40	gold quality
adrenal cortex	UBERON:0001235	96.39	gold quality
gluteal muscle	UBERON:0002000	96.38	gold quality
renal medulla	UBERON:0000362	96.32	gold quality
myocardium	UBERON:0002349	96.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting IMMT, 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-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-506-5P	98.02	67.41	1065

Literature-anchored findings (GeneRIF, showing 23)

• Data show that the nuclear matrix protein matrin 3, cytoskeletal motor protein HMP, and the circadian clock protein lark were significantly decreased in fetal Down syndrome brain. (PMID:12469345)
• mitofilin is a critical organizer of the mitochondrial cristae morphology and thus indispensable for normal mitochondrial function (PMID:15647377)
• role in protein import related to maintenance of mitochondrial structure is suggested; mitofilin helps regulate mitochondrial morphology and four of the associated proteins (metaxins 1 and 2, SAM50 and CHCHD3) have been implicated in protein import (PMID:17624330)
• The mitochondrial dysfunction induced by DISC1 deficiency was partially reversed by coexpression of Mitofilin, confirming a functional link between DISC1 and Mitofilin for the normal mitochondrial function. (PMID:20880836)
• CHCM1/CHCHD6, novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology. (PMID:22228767)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• mitofilin distinctly functions in mitochondrial cristae remodeling and controls cytochrome c release during apoptosis. (PMID:23058921)
• APOOL is a cardiolipin-binding component of the Mitofilin/MINOS protein complex. (PMID:23704930)
• Mitofilin, a mitochondria protein, is shown to be related to cardiac hypertrophy for the first time, which enhances our understanding of the role of mitochondria in cardiac hypertrophy. (PMID:24555791)
• Transgenic overexpression of mitofilin preserves mitochondrial structure, leading to restoration of mitochondrial function and attenuation of cardiac contractile dysfunction in the diabetic heart. (PMID:25463274)
• Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription. (PMID:25612828)
• Mitofilin-knockdown cells showed decreased mitochondrial membrane potential (DeltaPsim) and intracellular ATP content, which were minimally affected in CHCHD6-knockout cells. (PMID:26530328)
• PKA-mediated phosphorylation of MIC60 negatively regulates mitochondrial clearance that is initiated by PINK1 and Parkin. (PMID:27153535)
• Sub-mitochondrial localization of the genetic-tagged mitochondrial intermembrane space-bridging components Mic19, Mic60 and Sam50. (PMID:28808085)
• It analyses revealed that Trak1 interacts and colocalizes with mitofusins on the outer mitochondrial membrane and functions with mitofusins to promote mitochondrial tethering and fusion. (PMID:28924745)
• Mitofilin, apoptosis-inducing factor (AIF) and poly(ADP-ribose) polymerase (PARP) expression were measured by Western blot analysis. (PMID:29489384)
• Pediatric ependymoma: GNAO1, ASAH1, IMMT and IPO7 protein expression and 5-year prognosis correlation. (PMID:31505435)
• Study demonstrated that high-IMMT expression is related to some clinicopathological parameters of patients with lung adenocarcinoma, and that its expression is an independent prognostic predictor of poorer survival. (PMID:31583841)
• CHCHD10-regulated OPA1-mitofilin complex mediates TDP-43-induced mitochondrial phenotypes associated with frontotemporal dementia. (PMID:32369233)
• Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins. (PMID:32788360)
• Conserved GxxxG and WN motifs of MIC13 are essential for bridging two MICOS subcomplexes. (PMID:34271005)
• Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants in IMMT gene. (PMID:34842280)
• Suppressing mitochondrial inner membrane protein (IMMT) inhibits the proliferation of breast cancer cells through mitochondrial remodeling and metabolic regulation. (PMID:38834715)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	immt	ENSDARG00000102874
mus_musculus	Immt	ENSMUSG00000052337
rattus_norvegicus	Immt	ENSRNOG00000009097
drosophila_melanogaster	Mitofilin	FBGN0019960
caenorhabditis_elegans		WBGENE00012315
caenorhabditis_elegans		WBGENE00020511

Protein

Protein identifiers

MICOS complex subunit MIC60 — Q16891 (reviewed: Q16891)

Alternative names: Cell proliferation-inducing gene 4/52 protein, Mitochondrial inner membrane protein, Mitofilin, p87/89

All UniProt accessions (5): Q16891, B9A067, C9J406, D6RAW4, H7C463

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology.

Subunit / interactions. Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with HSPA1A/HSPA1B and OPA1, preferentially with the soluble OPA1 form. Interacts with MICOS13/MIC13, MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, SAMM50 and TMEM11. Interacts with APOO/MIC23/MIC26 and APOOL/MIC27. Interacts with ARMC1. Interacts with ARMC12. Interacts with mitochondrial microprotein SHMOOSE. (Microbial infection) Interacts with human cytomegalovirus protein UL13; this interaction alters cristae architecture.

Subcellular location. Mitochondrion inner membrane. Mitochondrion.

Similarity. Belongs to the MICOS complex subunit Mic60 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q16891-1	1	yes
Q16891-2	2
Q16891-3	3
Q16891-4	4

RefSeq proteins (47): NP_001093639, NP_001093640, NP_001387015, NP_001387016, NP_001387017, NP_001387018, NP_001387019, NP_001387020, NP_001387029, NP_001387030, NP_001387031, NP_001387032, NP_001387033, NP_001387034, NP_001387035, NP_001387036, NP_001387037, NP_001387038, NP_001387039, NP_001387040, NP_001387041, NP_001387042, NP_001387043, NP_001387044, NP_001387045, NP_001387046, NP_001387047, NP_001387048, NP_001387049, NP_001387050, NP_001387051, NP_001387052, NP_001387053, NP_001387054, NP_001387055, NP_001387056, NP_001387057, NP_001387058, NP_001387059, NP_001387060, NP_001387061, NP_001387062, NP_001387063, NP_001387064, NP_001387066, NP_001387067, NP_006830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019133	MIC60	Family

Pfam: PF09731

UniProt features (33 total): sequence conflict 11, modified residue 9, splice variant 3, topological domain 2, sequence variant 2, region of interest 2, transit peptide 1, chain 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9QWR	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16891-F1	74.81	0.32

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 (9): 113, 211, 222, 223, 388, 390, 451, 103, 112

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8949613	Cristae formation
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance

MSigDB gene sets: 245 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_DNMT1, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, MORF_BUB1, LFA1_Q6, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, AACYNNNNTTCCS_UNKNOWN, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_CRISTAE_FORMATION, ATGTTAA_MIR302C

GO Biological Process (4): inner mitochondrial membrane organization (GO:0007007), cristae formation (GO:0042407), mitochondrial calcium ion homeostasis (GO:0051560), neuron cellular homeostasis (GO:0070050)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (9): SAM complex (GO:0001401), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), membrane (GO:0016020), mitochondrial crista junction (GO:0044284), MICOS complex (GO:0061617), MIB complex (GO:0140275), mitochondrial envelope (GO:0005740)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
inner mitochondrial membrane protein complex	2
mitochondrial membrane organization	1
inner mitochondrial membrane organization	1
intracellular calcium ion homeostasis	1
cellular homeostasis	1
nucleic acid binding	1
binding	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
cellular anatomical structure	1
mitochondrial inner membrane	1
organelle membrane contact site	1
organelle envelope	1

Protein interactions and networks

STRING

2934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMMT	CHCHD3	Q9NX63	998
IMMT	CHCHD6	Q9BRQ6	994
IMMT	PIK3CG	P48736	992
IMMT	APOO	Q9BUR5	989
IMMT	APOOL	Q6UXV4	985
IMMT	MICOS10	Q5TGZ0	975
IMMT	SAMM50	Q9Y512	967
IMMT	MICOS13	Q5XKP0	937
IMMT	PUF60	Q9UHX1	878
IMMT	PIK3R5	Q8WYR1	854
IMMT	ERCC2	P18074	850
IMMT	OXA1L	Q15070	848
IMMT	VDAC1	P21796	848
IMMT	PPP1R12C	Q9BZL4	847
IMMT	MPV17	P39210	844

IntAct

356 interactions, top by confidence:

A	B	Type	Score
EXOC6	EXOC5	psi-mi:“MI:0914”(association)	0.840
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HTT	IMMT	psi-mi:“MI:0915”(physical association)	0.670
CHCHD10	IMMT	psi-mi:“MI:0915”(physical association)	0.600
IMMT	CHCHD10	psi-mi:“MI:0914”(association)	0.600
IMMT	CHCHD10	psi-mi:“MI:0915”(physical association)	0.600
IMMT	CHCHD10	psi-mi:“MI:2364”(proximity)	0.600
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
PDE4DIP	IMMT	psi-mi:“MI:0915”(physical association)	0.570
IMMT		psi-mi:“MI:0915”(physical association)	0.560
	IMMT	psi-mi:“MI:0915”(physical association)	0.540
	IMMT	psi-mi:“MI:0407”(direct interaction)	0.540
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530

BioGRID (676): IMMT (Affinity Capture-MS), IMMT (Affinity Capture-Western), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Affinity Capture-MS), IMMT (Two-hybrid), IMMT (Affinity Capture-MS), IMMT (Co-fractionation)

ESM2 similar proteins: A0A1S4D1D3, A0A1W2PR95, A1D9I5, A5D796, A7SD85, B0W6N3, D2K8N5, E1C760, E7EXT2, F7AEX0, O08836, O57476, P51951, P54729, P78318, P92948, Q0CU99, Q16543, Q16891, Q173M7, Q1DM35, Q2PIU8, Q2QY04, Q3ZC62, Q4V8E4, Q4W9M7, Q5AXH3, Q5EAC6, Q5M990, Q5PQS7, Q61081, Q61249, Q63692, Q6PID6, Q7SYB2, Q8C6E0, Q8CAQ8, Q8LDQ4, Q8R3N6, Q93VM9

Diamond homologs: Q16891, Q3KR86, Q8CAQ8, Q6BXM9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IMMT	“up-regulates activity”	PINK1	binding
PRKACA	“down-regulates activity”	IMMT	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein import	8	12.1×	2e-04
MAPK6/MAPK4 signaling	7	8.6×	4e-03
Mitochondrial protein degradation	8	8.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete protein targeting to mitochondrion	6	25.3×	7e-05
mitochondrion organization	10	11.0×	3e-05
positive regulation of neuron projection development	8	7.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2169 predictions. Top by Δscore:

Variant	Effect	Δscore
2:86144879:GGCC:G	acceptor_loss	1.0000
2:86144881:CCT:C	acceptor_loss	1.0000
2:86144882:CTAC:C	acceptor_loss	1.0000
2:86146056:G:C	donor_gain	1.0000
2:86146062:GCTTA:G	donor_loss	1.0000
2:86146063:CTTAC:C	donor_loss	1.0000
2:86146064:TTA:T	donor_loss	1.0000
2:86146065:TAC:T	donor_loss	1.0000
2:86146066:A:AC	donor_gain	1.0000
2:86146066:ACT:A	donor_gain	1.0000
2:86146067:C:CG	donor_gain	1.0000
2:86146067:CT:C	donor_gain	1.0000
2:86146067:CTC:C	donor_gain	1.0000
2:86146067:CTCT:C	donor_gain	1.0000
2:86146067:CTCTG:C	donor_gain	1.0000
2:86146069:CTGA:C	donor_gain	1.0000
2:86146193:AGGTT:A	acceptor_gain	1.0000
2:86146194:GGTT:G	acceptor_gain	1.0000
2:86146195:GTT:G	acceptor_gain	1.0000
2:86146196:TT:T	acceptor_gain	1.0000
2:86146197:TCTG:T	acceptor_loss	1.0000
2:86146198:C:CC	acceptor_gain	1.0000
2:86146198:C:CG	acceptor_loss	1.0000
2:86146199:T:C	acceptor_loss	1.0000
2:86146203:A:AC	acceptor_gain	1.0000
2:86146203:A:C	acceptor_gain	1.0000
2:86146210:A:T	acceptor_gain	1.0000
2:86147269:T:C	acceptor_gain	1.0000
2:86147654:AAT:A	donor_gain	1.0000
2:86147696:CCTCA:C	donor_loss	1.0000

AlphaMissense

4910 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:86144375:A:G	W724R	0.999
2:86144375:A:T	W724R	0.999
2:86147776:C:G	A487P	0.999
2:86147781:C:G	R485P	0.999
2:86147787:A:G	L483P	0.999
2:86151476:C:G	A408P	0.999
2:86147773:C:G	A488P	0.998
2:86151466:C:G	R411P	0.998
2:86146077:C:G	A552P	0.997
2:86146094:A:G	L546P	0.997
2:86151454:A:G	L415P	0.997
2:86144373:C:A	W724C	0.996
2:86144373:C:G	W724C	0.996
2:86144407:A:G	L713P	0.996
2:86147769:G:T	A489D	0.996
2:86147770:C:G	A489P	0.996
2:86147784:C:G	R484P	0.996
2:86151469:C:G	R410P	0.996
2:86151487:A:G	L404P	0.996
2:86144306:C:G	A747P	0.995
2:86144311:G:T	A745D	0.995
2:86144363:C:G	A728P	0.995
2:86144464:G:T	A694D	0.995
2:86146107:C:G	A542P	0.995
2:86147742:A:G	L498P	0.995
2:86147778:T:G	Q486P	0.995
2:86144350:A:G	L732P	0.994
2:86144426:C:G	A707P	0.994
2:86144428:G:T	A706E	0.994
2:86144653:A:G	L631P	0.994

dbSNP variants (sampled 300 via entrez): RS1000118306 (2:86168503 G>C), RS1000142664 (2:86155116 G>T), RS1000178117 (2:86174260 T>A), RS1000277265 (2:86161450 G>A), RS1000367639 (2:86175491 A>G), RS1000384498 (2:86154931 C>T), RS1000527794 (2:86156358 G>A), RS1000653640 (2:86180633 T>C), RS1000886812 (2:86148407 G>A,C), RS1000892618 (2:86182981 G>A,C,T), RS1000901796 (2:86166320 G>A), RS1001030693 (2:86195387 G>A,C), RS1001040793 (2:86195169 G>A), RS1001066573 (2:86159413 G>A,T), RS1001118744 (2:86166636 T>C)

Disease associations

OMIM: gene MIM:600378 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_125	Night sleep phenotypes	5.000000e-06
GCST004730_1	Facial emotion recognition (sad faces)	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105768 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.13	Kd	7.429	nM	CHEMBL5653589
8.13	ED50	7.429	nM	CHEMBL5653589
5.24	Kd	5746	nM	CHEMBL3752910
5.24	ED50	5746	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148586: Binding affinity to human IMMT incubated for 45 mins by Kinobead based pull down assay	kd	0.0074	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148586: Binding affinity to human IMMT incubated for 45 mins by Kinobead based pull down assay	kd	5.7461	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	decreases expression, increases expression, affects cotreatment	2
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Quercetin	decreases expression, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
beauvericin	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
cadmium sulfate	decreases expression	1
microcystin RR	decreases expression, increases expression	1
di-n-butylphosphoric acid	affects expression	1
enniatins	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Irinotecan	affects expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012554	Binding	Binding affinity to MICOS complex subunit MIC60 in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SS54	HAP1 IMMT (-) 1	Cancer cell line	Male
CVCL_SS55	HAP1 IMMT (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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