BRINP2

Summary

BRINP2 (BMP/retinoic acid inducible neural specific 2, HGNC:13746) is a protein-coding gene on chromosome 1q25.2, encoding BMP/retinoic acid-inducible neural-specific protein 2 (Q9C0B6). Inhibits neuronal cell proliferation by negative regulation of the cell cycle transition.

Predicted to be involved in cellular response to retinoic acid; central nervous system neuron differentiation; and negative regulation of mitotic cell cycle. Predicted to act upstream of or within locomotion and nervous system development. Predicted to be located in extracellular region. Predicted to be active in cytoplasm; dendrite; and neuronal cell body. Implicated in oral squamous cell carcinoma.

Source: NCBI Gene 57795 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_021165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13746
Approved symbol	BRINP2
Name	BMP/retinoic acid inducible neural specific 2
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Aliases	DBCCR1L2
Ensembl gene	ENSG00000198797
Ensembl biotype	protein_coding
OMIM	619359
Entrez	57795

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000361539, ENST00000460161, ENST00000478325, ENST00000907914, ENST00000907915, ENST00000926433, ENST00000926434, ENST00000926435, ENST00000944005, ENST00000944006, ENST00000944007, ENST00000944008, ENST00000944009, ENST00000944010

RefSeq mRNA: 1 — MANE Select: NM_021165 NM_021165

CCDS: CCDS1320

Canonical transcript exons

ENST00000361539 — 8 exons

Exon	Start	End
ENSE00000790030	177255919	177256109
ENSE00001161596	177170958	177171732
ENSE00001166070	177280412	177282422
ENSE00002372804	177257176	177257384
ENSE00002694274	177229801	177230145
ENSE00003470915	177276198	177276434
ENSE00003560791	177278563	177278785
ENSE00003626515	177273488	177273593

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 89.24.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3200 / max 215.8186, expressed in 220 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6852	1.8571	184
6853	1.4135	165
6854	0.0494	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	89.24	gold quality
prefrontal cortex	UBERON:0000451	88.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.01	gold quality
middle temporal gyrus	UBERON:0002771	87.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.14	gold quality
frontal cortex	UBERON:0001870	86.91	gold quality
primary visual cortex	UBERON:0002436	86.76	gold quality
cingulate cortex	UBERON:0003027	86.63	gold quality
anterior cingulate cortex	UBERON:0009835	86.49	gold quality
amygdala	UBERON:0001876	86.43	gold quality
neocortex	UBERON:0001950	86.43	gold quality
temporal lobe	UBERON:0001871	85.41	gold quality
cerebral cortex	UBERON:0000956	85.29	gold quality
superior frontal gyrus	UBERON:0002661	84.72	gold quality
entorhinal cortex	UBERON:0002728	84.50	gold quality
Brodmann (1909) area 46	UBERON:0006483	84.43	gold quality
occipital lobe	UBERON:0002021	83.91	gold quality
telencephalon	UBERON:0001893	83.65	gold quality
postcentral gyrus	UBERON:0002581	82.83	gold quality
nucleus accumbens	UBERON:0001882	82.82	gold quality
right adrenal gland cortex	UBERON:0035827	82.55	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.19	gold quality
forebrain	UBERON:0001890	82.14	gold quality
left adrenal gland	UBERON:0001234	81.91	gold quality
left adrenal gland cortex	UBERON:0035825	81.86	gold quality
right adrenal gland	UBERON:0001233	81.81	gold quality
parietal lobe	UBERON:0001872	81.60	gold quality
orbitofrontal cortex	UBERON:0004167	81.57	gold quality
adrenal cortex	UBERON:0001235	81.27	gold quality
Brodmann (1909) area 10	UBERON:0013541	80.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting BRINP2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6887-3P	99.66	67.83	1778

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	brinp2	ENSDARG00000014302
danio_rerio	brinp3b	ENSDARG00000075352
danio_rerio	brinp3a.1	ENSDARG00000076351
mus_musculus	Brinp2	ENSMUSG00000004031
rattus_norvegicus	Brinp2	ENSRNOG00000005592

Paralogs (2): BRINP1 (ENSG00000078725), BRINP3 (ENSG00000162670)

Protein

Protein identifiers

BMP/retinoic acid-inducible neural-specific protein 2 — Q9C0B6 (reviewed: Q9C0B6)

Alternative names: DBCCR1-like protein 2

All UniProt accessions (1): Q9C0B6

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits neuronal cell proliferation by negative regulation of the cell cycle transition.

Subcellular location. Secreted.

Similarity. Belongs to the BRINP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0B6-1	1	yes
Q9C0B6-2	2

RefSeq proteins (1): NP_066988* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020864	MACPF	Domain
IPR033237	BRINP	Family
IPR057450	BRINP_EGF	Domain
IPR057671	BRINP_C	Domain

Pfam: PF01823, PF19052, PF25415

UniProt features (12 total): glycosylation site 6, sequence variant 2, signal peptide 1, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0B6-F1	76.72	0.20

Functional residue map

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

Glycosylation sites (6): 185, 354, 473, 579, 626, 658

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_RETINOIC_ACID, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (9): central nervous system neuron differentiation (GO:0021953), multicellular organism growth (GO:0035264), locomotion (GO:0040011), positive regulation of neuron differentiation (GO:0045666), negative regulation of mitotic cell cycle (GO:0045930), cellular response to retinoic acid (GO:0071300), nervous system development (GO:0007399), negative regulation of cell cycle (GO:0045786), regulation of cell cycle (GO:0051726)

GO Molecular Function (0):

GO Cellular Component (4): extracellular region (GO:0005576), cytoplasm (GO:0005737), dendrite (GO:0030425), neuronal cell body (GO:0043025)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron differentiation	2
cell cycle	2
cellular anatomical structure	2
central nervous system development	1
multicellular organismal process	1
developmental growth	1
biological_process	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
negative regulation of cell cycle	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
system development	1
negative regulation of cellular process	1
regulation of cell cycle	1
regulation of cellular process	1
intracellular anatomical structure	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRINP2	ASTN1	O14525	447
BRINP2	C19orf81	C9J6K1	446
BRINP2	PPIL1	Q9Y3C6	389
BRINP2	C6orf118	Q5T5N4	379
BRINP2	ASTN2	O75129	373
BRINP2	ISLR2	Q6UXK2	370
BRINP2	CXXC5	Q7LFL8	360
BRINP2	FAM171A2	A8MVW0	349
BRINP2	ZBED11	P0CF97	348
BRINP2	LRPAP1	P30533	346
BRINP2	SLIT3	O75094	334
BRINP2	RWDD4	Q6NW29	325
BRINP2	GARIN3	Q8TC56	324
BRINP2	IGSF8	Q969P0	321
BRINP2	FAM86C1P	Q9NVL1	320

IntAct

7 interactions, top by confidence:

A	B	Type	Score
BRINP3	BUB1	psi-mi:“MI:0914”(association)	0.530
BRINP2	ATP5MC1	psi-mi:“MI:0914”(association)	0.530
SDCBP	BRINP2	psi-mi:“MI:0407”(direct interaction)	0.440
BRINP2	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): RDH14 (Affinity Capture-MS), BRINP2 (Affinity Capture-MS), ATP5G1 (Affinity Capture-MS), CANX (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), RDH14 (Affinity Capture-MS), BRINP2 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), CANX (Affinity Capture-MS), ATP5G1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), SPG7 (Affinity Capture-MS), GALNT1 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YXX9, A0A1Z2R986, A2RTF1, C6KI89, E9Q355, F5HFJ7, O36400, P03425, P04853, P09258, P09728, P0DP43, P12554, P12556, P16772, P19758, P21526, P22229, P28907, P35740, P35771, Q04547, Q2TAV2, Q2YDM0, Q3TBN1, Q499E0, Q4R6B2, Q5BKX0, Q5E9L2, Q5RDR5, Q66000, Q66001, Q68FB2, Q6AY76, Q6DFY8, Q6ZRH7, Q76B58, Q77MP7, Q77NN4, Q783Y1

Diamond homologs: O60477, Q499E0, Q5E9L2, Q5RDR5, Q6DFY8, Q76B58, Q7ZZR3, Q8K1M7, Q8K1M8, Q920P3, Q925T8, Q9C0B6, Q90X85

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	105
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1716 predictions. Top by Δscore:

Variant	Effect	Δscore
1:177209595:A:AG	acceptor_gain	1.0000
1:177209596:G:GG	acceptor_gain	1.0000
1:177255918:GGGA:G	acceptor_gain	1.0000
1:177256072:G:GG	donor_gain	1.0000
1:177257381:CAAGG:C	donor_loss	1.0000
1:177257382:AAGG:A	donor_loss	1.0000
1:177257383:AGGTA:A	donor_loss	1.0000
1:177257384:GGTA:G	donor_loss	1.0000
1:177257385:GTAAT:G	donor_loss	1.0000
1:177257386:T:G	donor_loss	1.0000
1:177273594:G:GG	donor_gain	1.0000
1:177276196:A:AG	acceptor_gain	1.0000
1:177276197:G:GG	acceptor_gain	1.0000
1:177276197:GGC:G	acceptor_gain	1.0000
1:177276430:GTCAG:G	donor_gain	1.0000
1:177276432:CAGGT:C	donor_loss	1.0000
1:177276433:AG:A	donor_loss	1.0000
1:177276434:GG:G	donor_loss	1.0000
1:177276435:G:A	donor_loss	1.0000
1:177276436:T:G	donor_loss	1.0000
1:177278561:A:AG	acceptor_gain	1.0000
1:177278561:AGA:A	acceptor_loss	1.0000
1:177278562:G:GA	acceptor_gain	1.0000
1:177278562:GA:G	acceptor_gain	1.0000
1:177278562:GAA:G	acceptor_gain	1.0000
1:177278562:GAAGA:G	acceptor_gain	1.0000
1:177278781:GAGAG:G	donor_gain	1.0000
1:177278782:AGAGG:A	donor_loss	1.0000
1:177278783:GAG:G	donor_gain	1.0000
1:177278786:G:GA	donor_loss	1.0000

AlphaMissense

5137 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:177255932:T:A	W95R	1.000
1:177255932:T:C	W95R	1.000
1:177257188:T:C	L158P	1.000
1:177280841:G:C	K555N	1.000
1:177280841:G:T	K555N	1.000
1:177280949:C:A	N591K	1.000
1:177280949:C:G	N591K	1.000
1:177280965:C:G	H597D	1.000
1:177281095:A:T	E640V	1.000
1:177281101:T:A	V642D	1.000
1:177281335:T:C	L720P	1.000
1:177281403:T:C	C743R	1.000
1:177281520:T:C	C782R	1.000
1:177230145:G:T	R90M	0.999
1:177255923:T:C	F92L	0.999
1:177255925:T:A	F92L	0.999
1:177255925:T:G	F92L	0.999
1:177255934:G:C	W95C	0.999
1:177255934:G:T	W95C	0.999
1:177257184:T:C	S157P	0.999
1:177257308:C:A	A198D	0.999
1:177257316:T:G	Y201D	0.999
1:177257319:T:C	F202L	0.999
1:177257320:T:C	F202S	0.999
1:177257320:T:G	F202C	0.999
1:177257321:C:A	F202L	0.999
1:177257321:C:G	F202L	0.999
1:177257350:T:C	L212P	0.999
1:177273518:T:C	C234R	0.999
1:177280647:T:A	C491S	0.999

dbSNP variants (sampled 300 via entrez): RS1000006275 (1:177261915 C>A,G), RS1000012976 (1:177187101 T>G), RS1000104675 (1:177232642 C>T), RS1000137075 (1:177277305 T>A,C), RS1000140217 (1:177189442 A>G), RS1000147523 (1:177205188 G>A), RS1000161177 (1:177249598 T>A), RS1000180538 (1:177204819 T>C), RS1000194522 (1:177225206 T>C), RS1000246539 (1:177185101 G>A), RS1000248586 (1:177202340 G>C), RS1000252604 (1:177258707 C>T), RS1000295368 (1:177214877 C>T), RS1000339101 (1:177242967 T>A), RS1000356544 (1:177173569 G>A,C)

Disease associations

OMIM: gene MIM:619359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002539_33	Schizophrenia	4.000000e-08
GCST003993_34	Menarche (age at onset)	5.000000e-11
GCST004521_238	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST004946_11	Schizophrenia	3.000000e-09
GCST006041_21	Major depressive disorder	8.000000e-08
GCST006803_82	Schizophrenia	1.000000e-08
GCST007201_434	Schizophrenia	8.000000e-08
GCST007201_86	Schizophrenia	4.000000e-11
GCST012676_1	Body composition traits	1.000000e-06
GCST012676_2	Body composition traits	8.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007800	body fat percentage

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	2
Aflatoxin B1	decreases methylation	2
bisphenol A	decreases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
fipronil	affects cotreatment, increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
DEET	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Acrylamide	decreases expression	1
Raloxifene Hydrochloride	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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