IMMP1L

Summary

IMMP1L (inner mitochondrial membrane peptidase subunit 1, HGNC:26317) is a protein-coding gene on chromosome 11p13, encoding Mitochondrial inner membrane protease subunit 1 (Q96LU5). Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space.

The mitochondrial inner membrane peptidase (IMP) complex generates mature, active proteins in the mitochondrial intermembrane space by proteolytically removing the mitochondrial targeting presequence of nuclear-encoded proteins. IMP1 and IMP2 (IMMP2L; MIM 605977) are the catalytic subunits of the IMP complex (Burri et al., 2005 [PubMed 15814844]).

Source: NCBI Gene 196294 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 37 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001304274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26317
Approved symbol	IMMP1L
Name	inner mitochondrial membrane peptidase subunit 1
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25059
Ensembl gene	ENSG00000148950
Ensembl biotype	protein_coding
OMIM	612323
Entrez	196294

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 21 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000278200, ENST00000526776, ENST00000527184, ENST00000528161, ENST00000529749, ENST00000530023, ENST00000531331, ENST00000531693, ENST00000532287, ENST00000532624, ENST00000532668, ENST00000533512, ENST00000533642, ENST00000533921, ENST00000534812, ENST00000648582, ENST00000873558, ENST00000873559, ENST00000873560, ENST00000873561, ENST00000873562, ENST00000873563, ENST00000873564, ENST00000873565, ENST00000922648, ENST00000922649, ENST00000922650, ENST00000922651, ENST00000922652, ENST00000946558

RefSeq mRNA: 2 — MANE Select: NM_001304274 NM_001304274, NM_144981

CCDS: CCDS7874

Canonical transcript exons

ENST00000532287 — 6 exons

Exon	Start	End
ENSE00001004086	31509519	31509622
ENSE00003493618	31463172	31463305
ENSE00003508102	31460626	31460714
ENSE00003614011	31433460	31433570
ENSE00003673774	31432401	31432568
ENSE00003790566	31456260	31456386

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.4215 / max 198.4478, expressed in 1754 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119129	12.2149	1754
119128	0.2066	91

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	96.01	gold quality
islet of Langerhans	UBERON:0000006	94.40	gold quality
ventricular zone	UBERON:0003053	94.08	gold quality
cerebellar hemisphere	UBERON:0002245	93.95	gold quality
cerebellar cortex	UBERON:0002129	93.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.57	gold quality
cerebellum	UBERON:0002037	93.16	gold quality
caudate nucleus	UBERON:0001873	93.03	gold quality
nucleus accumbens	UBERON:0001882	92.98	gold quality
putamen	UBERON:0001874	92.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.00	gold quality
biceps brachii	UBERON:0001507	91.91	gold quality
adrenal tissue	UBERON:0018303	91.83	gold quality
prefrontal cortex	UBERON:0000451	91.65	gold quality
ganglionic eminence	UBERON:0004023	91.50	gold quality
adenohypophysis	UBERON:0002196	91.40	gold quality
anterior cingulate cortex	UBERON:0009835	91.30	gold quality
amygdala	UBERON:0001876	91.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.66	gold quality
pituitary gland	UBERON:0000007	90.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.38	gold quality
oocyte	CL:0000023	90.30	gold quality
muscle of leg	UBERON:0001383	90.22	gold quality
hypothalamus	UBERON:0001898	90.21	gold quality
right frontal lobe	UBERON:0002810	90.19	gold quality
mucosa of transverse colon	UBERON:0004991	90.19	gold quality
gastrocnemius	UBERON:0001388	89.99	gold quality
pancreas	UBERON:0001264	89.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting IMMP1L, 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-548P	99.98	72.25	3784
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-95-3P	89.95	66.87	81

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	immp1l	ENSDARG00000045935
mus_musculus	Immp1l	ENSMUSG00000042670
rattus_norvegicus	Immp1l	ENSRNOG00000004829
drosophila_melanogaster	CG9240	FBGN0030669
caenorhabditis_elegans		WBGENE00007021

Paralogs (1): IMMP2L (ENSG00000184903)

Protein

Protein identifiers

Mitochondrial inner membrane protease subunit 1 — Q96LU5 (reviewed: Q96LU5)

Alternative names: IMP1-like protein

All UniProt accessions (7): Q96LU5, A0A0B4J221, A0A3B3IS22, E9PIG6, E9PNR7, E9PR99, H0YD09

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO.

Subunit / interactions. Heterodimer of 2 subunits, IMMPL1 and IMMPL2.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the peptidase S26 family. IMP1 subfamily.

RefSeq proteins (2): NP_001291203, NP_659418 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000223	Pept_S26A_signal_pept_1	Family
IPR019533	Peptidase_S26	Domain
IPR036286	LexA/Signal_pep-like_sf	Homologous_superfamily
IPR052064	Mito_IMP1_subunit	Family

Pfam: PF10502

UniProt features (3 total): active site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LU5-F1	87.87	0.64

Functional residue map

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

Catalytic / active sites (2): 40; 83

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): GCANCTGNY_MYOD_Q6, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, CAGCTG_AP4_Q5, NKX61_01, GOBP_PROTEIN_MATURATION, OCT1_06, OCT1_07, GOCC_MITOCHONDRIAL_ENVELOPE, BASAKI_YBX1_TARGETS_UP, HAND1E47_01, ZHANG_BREAST_CANCER_PROGENITORS_UP, CART1_01, GOBP_PROTEIN_TARGETING_TO_MITOCHONDRION

GO Biological Process (3): obsolete signal peptide processing (GO:0006465), obsolete protein processing involved in protein targeting to mitochondrion (GO:0006627), proteolysis (GO:0006508)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial inner membrane peptidase complex (GO:0042720), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
inner mitochondrial membrane protein complex	1
serine-type endopeptidase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMMP1L	DNAJC24	Q6P3W2	923
IMMP1L	ELP4	Q96EB1	921
IMMP1L	DCDC1	P59894	907
IMMP1L	MPPED2	Q15777	872
IMMP1L	DIABLO	Q9NR28	764
IMMP1L	PAX6	P26367	625
IMMP1L	PMPCB	O75439	508
IMMP1L	ATP23	Q9Y6H3	504
IMMP1L	MIPEP	Q99797	483
IMMP1L	ZZEF1	O43149	480
IMMP1L	PMPCA	Q10713	477
IMMP1L	XPNPEP3	Q9NQH7	473
IMMP1L	KRT12	Q99456	468
IMMP1L	FSHB	P01225	452
IMMP1L	METAP1D	Q6UB28	441

IntAct

13 interactions, top by confidence:

A	B	Type	Score
FAM117B	GAPDHS	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
TSPAN5	KLHL2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
RAMP3	GOLIM4	psi-mi:“MI:0914”(association)	0.350
TM4SF5	PLSCR1	psi-mi:“MI:0914”(association)	0.350
CA6	PLXNA2	psi-mi:“MI:0914”(association)	0.350
IMMP1L	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
PARL	HAX1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (256): IMMP1L (Affinity Capture-MS), ZER1 (Affinity Capture-MS), IMMP1L (Affinity Capture-MS), IMMP1L (Affinity Capture-MS), IMMP1L (Affinity Capture-MS), IMMP1L (Proximity Label-MS), COX15 (Proximity Label-MS), IMMT (Proximity Label-MS), CLPB (Proximity Label-MS), ADCK2 (Proximity Label-MS), ACOT1 (Proximity Label-MS), IARS2 (Proximity Label-MS), GPD2 (Proximity Label-MS), SLC25A12 (Proximity Label-MS), SAMM50 (Proximity Label-MS)

ESM2 similar proteins: A1CL29, A1D6D8, A4RGA1, A7E716, B0D4L0, B0XWT3, B2B3T2, B6Q5G0, B8M5K5, C5G8L5, C5JJG5, C7ZHK5, C9S8G0, D5GNC3, D8Q7Q5, E3QXY4, E5A8D2, E9E796, E9F8V9, F0XJH4, O46504, O74800, P0C7V7, P13679, P28627, P42667, P46972, P67810, P67811, P67812, Q05AK6, Q0CQC5, Q28I39, Q2H1P3, Q2UBW3, Q4WYF4, Q5B8K4, Q5BIV4, Q5I047, Q5R9C7

Diamond homologs: O04348, O07560, P26844, P41025, P41027, P42668, P44454, P71013, P72660, P73157, P9WKA0, P9WKA1, Q51876, Q5BIV4, Q5HHB9, Q6NLT8, Q8H0W1, Q96LU5, Q9CQU8, Q9I5G7, Q9M9Z2, O74800, P0A1W2, P0A1W3, P28627, P28628, P46972, P57347, Q28I39, Q57350, Q5PQ63, Q6AZD4, Q8BPT6, Q9UST2, A8EXI2, A8F0M1, A8GM78, A8GQT7, A8GYE1, O25300

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
267191	NC_000011.8:g.31199000_31849000del650001	Pathogenic
563832	GRCh37/hg19 11p13(chr11:31466566-31714871)x1	Likely pathogenic

SpliceAI

1828 predictions. Top by Δscore:

Variant	Effect	Δscore
11:31433577:T:C	acceptor_gain	1.0000
11:31456259:CATAA:C	donor_gain	1.0000
11:31456387:C:CC	acceptor_gain	1.0000
11:31460713:CA:C	acceptor_gain	1.0000
11:31460715:C:CC	acceptor_gain	1.0000
11:31463165:AACTT:A	donor_loss	1.0000
11:31463166:ACTTA:A	donor_loss	1.0000
11:31463167:CTT:C	donor_loss	1.0000
11:31463168:TTAC:T	donor_loss	1.0000
11:31463169:TACC:T	donor_loss	1.0000
11:31463170:A:AC	donor_gain	1.0000
11:31463170:ACCAT:A	donor_loss	1.0000
11:31463171:C:CC	donor_gain	1.0000
11:31433455:GGTAC:G	donor_loss	0.9900
11:31433457:TACCT:T	donor_loss	0.9900
11:31433458:ACCT:A	donor_loss	0.9900
11:31433475:T:TA	donor_gain	0.9900
11:31433567:GCACC:G	acceptor_loss	0.9900
11:31433568:CACCT:C	acceptor_loss	0.9900
11:31433569:ACCT:A	acceptor_loss	0.9900
11:31433571:C:A	acceptor_loss	0.9900
11:31433571:C:CC	acceptor_gain	0.9900
11:31433572:T:G	acceptor_loss	0.9900
11:31448982:ATTT:A	donor_gain	0.9900
11:31448985:T:TA	donor_gain	0.9900
11:31456258:A:AC	donor_gain	0.9900
11:31456259:C:CC	donor_gain	0.9900
11:31456259:CATA:C	donor_gain	0.9900
11:31456263:A:C	donor_gain	0.9900
11:31456382:CACCT:C	acceptor_gain	0.9900

AlphaMissense

1091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:31456332:T:A	K83N	1.000
11:31456332:T:G	K83N	1.000
11:31433515:G:A	S126F	0.999
11:31433554:A:T	V113D	0.999
11:31456333:T:A	K83I	0.999
11:31433485:A:G	L136P	0.998
11:31433519:C:G	D125H	0.998
11:31433524:G:A	S123F	0.998
11:31433539:T:A	D118V	0.998
11:31433539:T:G	D118A	0.998
11:31433540:C:G	D118H	0.998
11:31433542:C:A	G117V	0.998
11:31433543:C:A	G117C	0.998
11:31433543:C:G	G117R	0.998
11:31456329:T:A	R84S	0.998
11:31456329:T:G	R84S	0.998
11:31456333:T:G	K83T	0.998
11:31456334:T:C	K83E	0.998
11:31460697:C:A	M41I	0.998
11:31460697:C:G	M41I	0.998
11:31460697:C:T	M41I	0.998
11:31433517:A:C	D125E	0.997
11:31433517:A:T	D125E	0.997
11:31433518:T:A	D125V	0.997
11:31433518:T:G	D125A	0.997
11:31433552:A:G	W114R	0.997
11:31433552:A:T	W114R	0.997
11:31433557:T:G	H112P	0.997
11:31456335:A:C	C82W	0.997
11:31456337:A:G	C82R	0.997

dbSNP variants (sampled 300 via entrez): RS1000013263 (11:31436468 T>C), RS1000039254 (11:31459013 C>T), RS1000047292 (11:31496200 T>C), RS1000232629 (11:31479160 C>A,T), RS1000247874 (11:31485576 A>T), RS1000254268 (11:31439020 A>G), RS1000336594 (11:31508879 A>T), RS1000337985 (11:31451177 G>C), RS1000343007 (11:31471806 C>T), RS1000453550 (11:31479487 G>A), RS1000471776 (11:31443030 C>A), RS1000486882 (11:31489408 T>A,C), RS1000551132 (11:31476390 T>C), RS1000553799 (11:31458449 T>C), RS1000562449 (11:31458785 G>A,C,T)

Disease associations

OMIM: gene MIM:612323 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): aniridia (MONDO:0019172)

Orphanet (1): OBSOLETE: Aniridia (Orphanet:77)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004076_21	Optic disc area	5.000000e-11
GCST004076_7	Optic disc area	2.000000e-10
GCST006976_109	Macular thickness	5.000000e-12
GCST009411_12	Optic disc area	8.000000e-11
GCST90026412_3	Severe autoimmune type 2 diabetes	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015783	Aniridia	C11.250.060; C11.270.060; C11.941.375.060; C16.131.384.079; C16.320.290.078

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Quercetin	decreases expression	1
Thimerosal	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9H8	Ubigene HEK293 IMMP1L KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02647359	PHASE2	COMPLETED	Study of Ataluren in Participants With Nonsense Mutation Aniridia
NCT04117880	PHASE2	WITHDRAWN	A Phase 2 Open Label Extension Study in Participants With Nonsense Mutation Aniridia
NCT05909735	PHASE1	COMPLETED	Treatment of LSCD With DM
NCT05044598	PHASE1/PHASE2	COMPLETED	RAFT - Clinical Trial of RAFT for Aniridia Related Keratopathy
NCT00001161	Not specified	COMPLETED	Abnormalities of the Eye’s Anterior Chamber, Iris, Cornea and Lens
NCT00265590	Not specified	COMPLETED	Correlation of Gene Abnormalities and Clinical Manifestations of Aniridia
NCT00503893	Not specified	UNKNOWN	Genetics of Wilms’ Tumor and/or the Associated Conditions of Aniridia, Hemihypertrophy, and Genitourinary Anomalies
NCT00758108	Not specified	COMPLETED	Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
NCT00812708	Not specified	COMPLETED	Clinical Evaluation of Morcher Artificial Iris Diaphragms
NCT01644552	Not specified	COMPLETED	Positive Angle Kappa
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02945176	Not specified	COMPLETED	Safety and Performance Study of the ARGOS-IO System in Patients Undergoing Boston Keratoprosthesis Implantation
NCT03461978	Not specified	COMPLETED	Ultrahigh-resolution Optical Coherence Tomography Imaging of the Anterior Eye Segment Structures
NCT03581864	Not specified	COMPLETED	Clinical Outcomes of Implantationof Black Diaphragm Intraocular Lens in Complete Aniridia and Aphakia Due to Posttraumatic Eye Rupture
NCT05390801	Not specified	RECRUITING	Congenital Aniridia Patient Questionnaire
NCT05400590	Not specified	RECRUITING	Comparison of the Healing Properties on Corneal Cells of Groth Factor-enriched Plasma and Autologous Serum From Aniridia Patients
NCT05562115	Not specified	COMPLETED	Proteomic Study of Tears From Patients With a PAX6 Mutation
NCT05954403	Not specified	RECRUITING	National Cohort on Congenital Defects of the Eye
NCT06412718	Not specified	UNKNOWN	Validation of Human Drugs Target of Repurposed Drugs and Novel Therapies
NCT06491615	Not specified	RECRUITING	National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases