MRNIP

Summary

MRNIP (MRN complex interacting protein, HGNC:30817) is a protein-coding gene on chromosome 5q35.3, encoding MRN complex-interacting protein (Q6NTE8). Plays a role in the cellular response to DNA damage and the maintenance of genome stability through its association with the MRN damage-sensing complex.

Enables chromatin binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of protein kinase activity; and regulation of double-strand break repair. Located in Mre11 complex and nucleoplasm.

Source: NCBI Gene 51149 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_016175

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30817
Approved symbol	MRNIP
Name	MRN complex interacting protein
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC65027, MGC78537, DKFZp686L2452, LOC51149
Ensembl gene	ENSG00000161010
Ensembl biotype	protein_coding
OMIM	617154
Entrez	51149

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 9 nonsense_mediated_decay, 7 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000292586, ENST00000376931, ENST00000517338, ENST00000518219, ENST00000518235, ENST00000518950, ENST00000519208, ENST00000519213, ENST00000519318, ENST00000519398, ENST00000520150, ENST00000520698, ENST00000520900, ENST00000520995, ENST00000521299, ENST00000521333, ENST00000521675, ENST00000522157, ENST00000522663, ENST00000523084, ENST00000523267, ENST00000523737, ENST00000523835, ENST00000524068

RefSeq mRNA: 2 — MANE Select: NM_016175 NM_001017987, NM_016175

CCDS: CCDS34318, CCDS34319

Canonical transcript exons

ENST00000292586 — 7 exons

Exon	Start	End
ENSE00002037864	179837276	179837885
ENSE00002119961	179858731	179858817
ENSE00003459050	179840872	179840959
ENSE00003466549	179853378	179853437
ENSE00003480526	179847978	179848066
ENSE00003595863	179841907	179842064
ENSE00003668878	179844152	179844227

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 97.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6897 / max 156.1556, expressed in 1694 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65263	11.3315	1691
65264	0.3582	187

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	97.21	gold quality
cerebellar cortex	UBERON:0002129	97.19	gold quality
cerebellum	UBERON:0002037	97.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.07	gold quality
right uterine tube	UBERON:0001302	95.80	gold quality
pituitary gland	UBERON:0000007	95.40	gold quality
adenohypophysis	UBERON:0002196	94.66	gold quality
left ovary	UBERON:0002119	94.64	gold quality
left lobe of thyroid gland	UBERON:0001120	94.63	gold quality
thyroid gland	UBERON:0002046	94.46	gold quality
right lobe of thyroid gland	UBERON:0001119	94.40	gold quality
endocervix	UBERON:0000458	94.17	gold quality
ovary	UBERON:0000992	94.12	gold quality
right ovary	UBERON:0002118	94.04	gold quality
mucosa of stomach	UBERON:0001199	93.68	gold quality
metanephros cortex	UBERON:0010533	93.34	gold quality
body of uterus	UBERON:0009853	92.96	gold quality
nerve	UBERON:0001021	92.94	gold quality
tibial nerve	UBERON:0001323	92.94	gold quality
spleen	UBERON:0002106	92.94	gold quality
uterine cervix	UBERON:0000002	92.84	gold quality
ectocervix	UBERON:0012249	92.73	gold quality
prostate gland	UBERON:0002367	92.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.47	gold quality
fallopian tube	UBERON:0003889	92.47	gold quality
cortex of kidney	UBERON:0001225	92.14	gold quality
right frontal lobe	UBERON:0002810	92.12	gold quality
fundus of stomach	UBERON:0001160	92.07	gold quality
descending thoracic aorta	UBERON:0002345	92.07	gold quality
hypothalamus	UBERON:0001898	92.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	48.59
E-ANND-3	yes	5.77
E-GEOD-81608	no	8.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting MRNIP, 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-5680	99.91	69.83	3421
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-218-2-3P	98.08	67.21	601
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-152-5P	96.42	66.59	960

Literature-anchored findings (GeneRIF, showing 1)

• these data reveal that MRNIP is an important component of the human DNA damage response. (PMID:27568553)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-177p5.2	ENSDARG00000074071
mus_musculus	Mrnip	ENSMUSG00000020381
rattus_norvegicus		ENSRNOG00000088971

Protein

Protein identifiers

MRN complex-interacting protein — Q6NTE8 (reviewed: Q6NTE8)

Alternative names: MRN-interacting protein

All UniProt accessions (13): Q6NTE8, B7Z1T6, E5RGF8, E5RHV0, E5RHY8, E5RI52, E5RIC8, E5RIJ7, E5RJC6, E5RK98, E7EMV9, F6UWW1, F6XPR0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the cellular response to DNA damage and the maintenance of genome stability through its association with the MRN damage-sensing complex. Promotes chromatin loading and activity of the MRN complex to facilitate subsequent ATM-mediated DNA damage response signaling and DNA repair.

Subunit / interactions. Associates with the MRE11-RAD50-NBN (MRN) damage-sensing complex; this association is constitutive. Interacts with MRE11. Interacts with NBN. Interacts with RAD50.

Subcellular location. Nucleus. Nucleoplasm.

Post-translational modifications. Phosphorylated; phosphorylation is constitutive and occurs in the absence of any DNA-damaging stimulus. Phosphorylation on Ser-115 is necessary for its nuclear retention.

Similarity. Belongs to the MRNIP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6NTE8-1	1	yes
Q6NTE8-2	2
Q6NTE8-3	3

RefSeq proteins (2): NP_001017987, NP_057259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032739	MRNIP	Family
IPR049472	MRNIP_N	Domain

Pfam: PF15749

UniProt features (29 total): mutagenesis site 8, region of interest 5, splice variant 4, sequence variant 4, compositionally biased region 3, modified residue 2, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NTE8-F1	56.91	0.15

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 (2): 100, 115

Mutagenesis-validated functional residues (8):

Position	Phenotype
100	does not affect nuclear localization. decreases weakly the association with the mrn complex. reduces phosphorylation; wh
115	reduces nuclear localization and increases dna damage accumulation. decreases weakly the association with the mrn comple
115	does not affect nuclear localization.
141	reduces nuclear localization and increases dna damage accumulation and does not affect the association with the mrn comp
143	reduces phosphorylation; when associated with a-100 and a-115.
148–151	decreases nuclear localization. reduces nuclear localization and increases dna damage accumulation and does not affect t
154	reduces nuclear localization and increases dna damage accumulation and does not affect the association with the mrn comp
213–237	reduces the association with the mrn complex.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_PHOSPHORYLATION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (8): DNA repair (GO:0006281), DNA damage response (GO:0006974), mitotic G2 DNA damage checkpoint signaling (GO:0007095), response to ionizing radiation (GO:0010212), positive regulation of protein kinase activity (GO:0045860), protein localization to chromatin (GO:0071168), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair via nonhomologous end joining (GO:2001032)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), Mre11 complex (GO:0030870)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
response to radiation	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
protein localization to chromosome	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
double-strand break repair via nonhomologous end joining	1
regulation of double-strand break repair	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

3623 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRNIP	RADX	Q6NSI4	531
MRNIP	SPIDR	Q14159	506
MRNIP	IQCC	Q4KMZ1	479
MRNIP	ZFYVE26	Q68DK2	471
MRNIP	RPL26L1	Q9UNX3	423
MRNIP	TOMM20L	Q6UXN7	392
MRNIP	MRPS9	P82933	391
MRNIP	HUS1B	Q8NHY5	375
MRNIP	ATMIN	O43313	371
MRNIP	ZNF396	Q96N95	371
MRNIP	RSRC1	Q96IZ7	360
MRNIP	EEF1G	P26641	353
MRNIP	YARS1	P54577	353
MRNIP	RPL22	P35268	350
MRNIP	RPS2	P15880	349
MRNIP	VARS1	P26640	349

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ANKRD44	ANKRD28	psi-mi:“MI:0914”(association)	0.710
NUTF2	MRNIP	psi-mi:“MI:0915”(physical association)	0.560
PSMB1	MRNIP	psi-mi:“MI:0915”(physical association)	0.560
MRNIP	PICK1	psi-mi:“MI:0915”(physical association)	0.560
MRNIP	NXF1	psi-mi:“MI:0915”(physical association)	0.560
MRNIP	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
MRNIP	DUSP23	psi-mi:“MI:0915”(physical association)	0.560
EIF3E	MRNIP	psi-mi:“MI:0915”(physical association)	0.560
EFHC1	MRNIP	psi-mi:“MI:0915”(physical association)	0.560
PKIA	MRNIP	psi-mi:“MI:0915”(physical association)	0.560
MRNIP	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
rep	AP3B1	psi-mi:“MI:0914”(association)	0.350
MIF	BLTP3B	psi-mi:“MI:0914”(association)	0.350
PSMB1	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
NUTF2	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
PICK1	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
NXF1	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
ENKD1	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
DUSP23	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
EIF3E	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
EFHC1	MRNIP	psi-mi:“MI:0915”(physical association)	0.000
PKIA	MRNIP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): C5orf45 (Two-hybrid), C5orf45 (Two-hybrid), C5orf45 (Two-hybrid), C5orf45 (Two-hybrid), C5orf45 (Two-hybrid), C5orf45 (Two-hybrid), C5orf45 (Two-hybrid), NXF1 (Two-hybrid), PKIA (Two-hybrid), C5orf45 (Affinity Capture-MS), C5orf45 (Affinity Capture-MS), C5orf45 (Affinity Capture-MS), C5orf45 (Affinity Capture-MS), C5orf45 (Proximity Label-MS), C5orf45 (Affinity Capture-MS)

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A6NDY2, A6NIJ5, A6NJQ4, A6NKC0, A6NNH2, A6NNJ1, A8MUA0, A8MWA6, A8MX19, A8MXJ8, A8MXZ1, A8MYA2, B1ASB6, D6RGX4, P0C7V4, P0C7W8, P0C7W9, P0C7X0, P0DV73, P0DV74, P0DV75, P0DV76, Q0VDD7, Q2KIS6, Q3UHD3, Q4R736, Q5SZB4, Q5T8A7, Q5VZ46, Q5XIK6, Q658T7, Q6A025, Q6NTE8, Q6PIX9, Q6ZMY3, Q86Y26, Q86YD7

Diamond homologs: Q32PP1, Q3ZBG8, Q6NTE8, Q9D1F5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1833 predictions. Top by Δscore:

Variant	Effect	Δscore
5:179836566:G:GG	donor_gain	1.0000
5:179853434:TTACC:T	acceptor_loss	1.0000
5:179853435:TACC:T	acceptor_loss	1.0000
5:179853436:ACCTG:A	acceptor_loss	1.0000
5:179853438:C:A	acceptor_loss	1.0000
5:179853439:T:G	acceptor_loss	1.0000
5:179858676:C:CA	donor_gain	1.0000
5:179858677:C:A	donor_gain	1.0000
5:179842061:TTTC:T	acceptor_gain	0.9900
5:179842062:TTCC:T	acceptor_loss	0.9900
5:179842063:TC:T	acceptor_gain	0.9900
5:179842064:CC:C	acceptor_gain	0.9900
5:179842065:C:CC	acceptor_gain	0.9900
5:179842066:T:A	acceptor_loss	0.9900
5:179842069:C:CT	acceptor_gain	0.9900
5:179842069:C:T	acceptor_gain	0.9900
5:179842070:A:T	acceptor_gain	0.9900
5:179842073:T:TC	acceptor_gain	0.9900
5:179853435:TAC:T	acceptor_gain	0.9900
5:179853438:C:CC	acceptor_gain	0.9900
5:179858768:AGCAC:A	donor_gain	0.9900
5:179858797:C:A	donor_gain	0.9900
5:179842060:TTTTC:T	acceptor_gain	0.9800
5:179842062:TTC:T	acceptor_gain	0.9800
5:179842072:A:C	acceptor_gain	0.9800
5:179842073:T:C	acceptor_gain	0.9800
5:179853275:CT:C	acceptor_gain	0.9800
5:179853434:TTAC:T	acceptor_gain	0.9800
5:179858726:CAGAC:C	donor_loss	0.9800
5:179858729:A:G	donor_loss	0.9800

AlphaMissense

2216 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:179853417:C:A	W29C	0.995
5:179853417:C:G	W29C	0.995
5:179858743:G:C	F18L	0.993
5:179858743:G:T	F18L	0.993
5:179858745:A:G	F18L	0.993
5:179853419:A:G	W29R	0.992
5:179853419:A:T	W29R	0.992
5:179848017:A:G	L59S	0.984
5:179848026:A:T	V56D	0.983
5:179858744:A:G	F18S	0.981
5:179848034:T:A	R53S	0.979
5:179848034:T:G	R53S	0.979
5:179848011:A:G	L61P	0.977
5:179858763:A:G	C12R	0.977
5:179848013:A:C	N60K	0.976
5:179848013:A:T	N60K	0.976
5:179848022:T:A	Q57H	0.975
5:179848022:T:G	Q57H	0.975
5:179853418:C:G	W29S	0.974
5:179858744:A:C	F18C	0.973
5:179853418:C:A	W29L	0.971
5:179853413:A:G	C31R	0.970
5:179853390:C:A	Q38H	0.969
5:179853390:C:G	Q38H	0.969
5:179848030:G:C	H55D	0.968
5:179848035:C:G	R53T	0.968
5:179848054:C:G	G47R	0.966
5:179858745:A:T	F18I	0.966
5:179858772:C:T	V9M	0.966
5:179853412:C:T	C31Y	0.965

dbSNP variants (sampled 300 via entrez): RS1000062187 (5:179859520 T>G), RS1000285529 (5:179840056 T>A), RS1000286819 (5:179857976 A>C), RS1000384630 (5:179844689 G>T), RS1000433238 (5:179859647 T>C), RS1000437136 (5:179844463 T>C), RS1000452395 (5:179843116 C>T), RS1000629936 (5:179840784 C>G,T), RS1000723038 (5:179851651 G>A), RS1000726977 (5:179845956 G>A), RS1000785792 (5:179850506 A>G,T), RS1000892504 (5:179846905 C>T), RS1000922119 (5:179839039 T>G), RS1001017776 (5:179857163 T>C,G), RS1001189658 (5:179842375 A>G)

Disease associations

OMIM: gene MIM:617154 | disease phenotypes: MIM:167250, MIM:617145

GenCC curated gene-disease

Mondo (2): Paget disease of bone 3 (MONDO:0008176), neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (MONDO:0014940)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002398_13	Neutrophil count	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10277	MRNIP, SQSTM1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Tretinoin	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Leflunomide	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases mutagenesis	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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