MINAR2

Summary

MINAR2 (membrane integral NOTCH2 associated receptor 2, HGNC:33914) is a protein-coding gene on chromosome 5q23.3, encoding Major intrinsically disordered NOTCH2-binding receptor 1-like (P59773). Binds cholesterol and may regulate the distribution and homeostasis of cholesterol in hair cells.

Enables cholesterol binding activity. Involved in angiogenesis. Located in endoplasmic reticulum. Implicated in autosomal recessive nonsyndromic deafness.

Source: NCBI Gene 100127206 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive 120 (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 9 total — 3 pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001257308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33914
Approved symbol	MINAR2
Name	membrane integral NOTCH2 associated receptor 2
Location	5q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186367
Ensembl biotype	protein_coding
OMIM	620215
Entrez	100127206

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000564719

RefSeq mRNA: 1 — MANE Select: NM_001257308 NM_001257308

CCDS: CCDS58966

Canonical transcript exons

ENST00000564719 — 3 exons

Exon	Start	End
ENSE00002024810	129760378	129760605
ENSE00002048030	129748094	129748355
ENSE00002585911	129764884	129766732

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 71.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0212 / max 12.1400, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58382	0.0212	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.38	silver quality
skeletal muscle tissue	UBERON:0001134	52.16	gold quality
sural nerve	UBERON:0015488	51.58	gold quality
muscle tissue	UBERON:0002385	50.86	gold quality
monocyte	CL:0000576	50.21	gold quality
leukocyte	CL:0000738	49.27	gold quality
duodenum	UBERON:0002114	46.35	silver quality
smooth muscle tissue	UBERON:0001135	45.13	gold quality
endometrium	UBERON:0001295	43.11	silver quality
adrenal tissue	UBERON:0018303	41.71	silver quality
body of uterus	UBERON:0009853	41.68	gold quality
ectocervix	UBERON:0012249	41.24	gold quality
placenta	UBERON:0001987	40.75	gold quality
ganglionic eminence	UBERON:0004023	40.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	40.58	silver quality
lower esophagus	UBERON:0013473	40.53	silver quality
bone marrow cell	CL:0002092	40.32	gold quality
hypothalamus	UBERON:0001898	40.18	gold quality
cortical plate	UBERON:0005343	40.07	gold quality
ventricular zone	UBERON:0003053	40.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	39.28	silver quality
lower esophagus mucosa	UBERON:0035834	38.75	gold quality
blood	UBERON:0000178	38.63	gold quality
bone marrow	UBERON:0002371	38.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	38.45	gold quality
left uterine tube	UBERON:0001303	38.42	gold quality
liver	UBERON:0002107	37.45	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
mucosa of transverse colon	UBERON:0004991	36.97	silver quality
granulocyte	CL:0000094	36.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.77

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice. (PMID:35727972)
• Inactivation of Minar2 in mice hyperactivates mTOR signaling and results in obesity. (PMID:37245847)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	minar2	ENSDARG00000078922
mus_musculus	Minar2	ENSMUSG00000050875
rattus_norvegicus	Minar2	ENSRNOG00000022429

Paralogs (1): MINAR1 (ENSG00000169330)

Protein

Protein identifiers

Major intrinsically disordered NOTCH2-binding receptor 1-like — P59773 (reviewed: P59773)

Alternative names: Major intrinsically disordered NOTCH2-associated receptor 2, Membrane integral NOTCH2-associated receptor 2

All UniProt accessions (1): P59773

UniProt curated annotations — full annotation on UniProt →

Function. Binds cholesterol and may regulate the distribution and homeostasis of cholesterol in hair cells. May play a role in angiogenesis.

Subunit / interactions. Interacts with NOTCH2.

Subcellular location. Lysosome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in the auditory hair cells.

Disease relevance. Deafness, autosomal recessive, 120 (DFNB120) [MIM:620238] A form of non-syndromic deafness characterized by congenital or prelingual onset of severe to profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the MINAR family.

RefSeq proteins (1): NP_001244237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009626	MINAR1-like_C	Domain
IPR039706	MINAR1-like	Family

Pfam: PF06789

UniProt features (8 total): glycosylation site 2, mutagenesis site 2, chain 1, transmembrane region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59773-F1	62.70	0.10

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 (1): 79

Glycosylation sites (2): 109, 125

Mutagenesis-validated functional residues (2):

Position	Phenotype
112	compromises cholesterol recruitment to the perinuclear region; when associated with a-117.
117	compromises cholesterol recruitment to the perinuclear region; when associated with a-112.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_STEROL_HOMEOSTASIS, GOCC_VACUOLAR_MEMBRANE, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_NEUROGENESIS, GOBP_LIPID_HOMEOSTASIS, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EAR_DEVELOPMENT, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_NEURON_APOPTOTIC_PROCESS, GOBP_MECHANORECEPTOR_DIFFERENTIATION, GOBP_HAIR_CELL_DIFFERENTIATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS

GO Biological Process (13): angiogenesis (GO:0001525), sensory perception of sound (GO:0007605), gene expression (GO:0010467), exploration behavior (GO:0035640), inner ear auditory receptor cell differentiation (GO:0042491), cholesterol homeostasis (GO:0042632), homeostasis of number of cells within a tissue (GO:0048873), neuron apoptotic process (GO:0051402), inner ear receptor cell stereocilium organization (GO:0060122), walking behavior (GO:0090659), apoptotic process (GO:0006915), locomotory behavior (GO:0007626), inner ear receptor cell differentiation (GO:0060113)

GO Molecular Function (2): cholesterol binding (GO:0015485), protein binding (GO:0005515)

GO Cellular Component (6): lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), stereocilium (GO:0032420), lysosome (GO:0005764), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
behavior	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
sensory perception of mechanical stimulus	1
macromolecule biosynthetic process	1
hair cell differentiation	1
inner ear receptor cell differentiation	1
sterol homeostasis	1
tissue homeostasis	1
homeostasis of number of cells	1
apoptotic process	1
neuron projection development	1
inner ear receptor cell development	1
locomotory behavior	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mechanoreceptor differentiation	1
inner ear development	1
sterol binding	1
alcohol binding	1
binding	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
stereocilium bundle	1
neuron projection	1
actin-based cell projection	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

76 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MINAR2	SPMIP10	Q6ZNM6	607
MINAR2	C5orf63	A6NC05	542
MINAR2	PRRC1	Q96M27	507
MINAR2	ISOC1	Q96CN7	479
MINAR2	GRAMD2B	Q96HH9	479
MINAR2	OCM2	P0CE71	435
MINAR2	MARCHF3	Q86UD3	432
MINAR2	ZNF608	Q9ULD9	418
MINAR2	CTXN3	Q4LDR2	417
MINAR2	ADAMTS19	Q8TE59	380
MINAR2	PHAX	Q9H814	371
MINAR2	RHOBTB3	O94955	352
MINAR2	SLC27A6	Q9Y2P4	322
MINAR2	CEP68	Q76N32	305
MINAR2	ADGRV1	Q8WXG9	276

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2VE00, A5PK14, F1QEA1, O75324, P0DKX4, P20826, P21581, P21583, P58550, P59773, P61807, P61808, P79169, P79368, Q06220, Q09108, Q10589, Q15053, Q17Q87, Q28132, Q28C41, Q28GJ0, Q29030, Q2T9X8, Q3UQS2, Q5PQQ9, Q5RBY6, Q5RKG1, Q5U3Z6, Q640L3, Q6AY06, Q6DF94, Q6IQY5, Q6NRX3, Q811A2, Q86YF9, Q8BIS8, Q8BMD2, Q8C804, Q8N0Z3

Diamond homologs: A0A140LFM6, D3ZJ47, F1QEA1, P59773, Q8C4X7, Q8K3V7, Q9UPX6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	1
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2443700	NM_001257308.2(MINAR2):c.144G>A (p.Trp48Ter)	Pathogenic
2443701	NM_001257308.2(MINAR2):c.412_419del (p.Arg138fs)	Pathogenic
2443702	NM_001257308.2(MINAR2):c.393G>T (p.Lys131Asn)	Pathogenic

SpliceAI

498 predictions. Top by Δscore:

Variant	Effect	Δscore
5:129748356:GTA:G	donor_loss	1.0000
5:129748357:T:A	donor_loss	1.0000
5:129758756:T:G	donor_gain	1.0000
5:129758756:T:TG	donor_gain	1.0000
5:129760644:GGAGA:G	donor_gain	0.9900
5:129760376:A:AG	acceptor_gain	0.9800
5:129760376:AGAG:A	acceptor_gain	0.9800
5:129760377:G:GG	acceptor_gain	0.9800
5:129760377:GA:G	acceptor_gain	0.9800
5:129760377:GAGG:G	acceptor_gain	0.9800
5:129758760:G:GG	donor_gain	0.9700
5:129760558:GAA:G	donor_gain	0.9700
5:129758759:A:AG	donor_gain	0.9600
5:129760376:AGAGG:A	acceptor_gain	0.9600
5:129760377:GAGGG:G	acceptor_gain	0.9600
5:129764883:GGAAA:G	acceptor_gain	0.9600
5:129764878:TTTTA:T	acceptor_loss	0.9500
5:129764879:TTTA:T	acceptor_loss	0.9500
5:129764880:TTAG:T	acceptor_loss	0.9500
5:129764881:TAGGA:T	acceptor_loss	0.9500
5:129764882:A:AG	acceptor_gain	0.9500
5:129764883:G:GG	acceptor_gain	0.9500
5:129748356:G:GG	donor_gain	0.9400
5:129748990:T:TG	donor_gain	0.9400
5:129758755:A:AG	donor_gain	0.9300
5:129758772:C:G	donor_gain	0.9300
5:129764868:T:TA	acceptor_loss	0.9200
5:129764883:GGA:G	acceptor_gain	0.9200
5:129758755:A:G	donor_gain	0.9100
5:129760372:TCTTA:T	acceptor_loss	0.9100

AlphaMissense

1251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:129764905:T:C	F139L	0.986
5:129764907:T:A	F139L	0.986
5:129764907:T:G	F139L	0.986
5:129764935:T:C	F149L	0.982
5:129764937:T:A	F149L	0.982
5:129764937:T:G	F149L	0.982
5:129764908:T:A	W140R	0.981
5:129764908:T:C	W140R	0.981
5:129764910:G:C	W140C	0.977
5:129764910:G:T	W140C	0.977
5:129760548:G:C	W112C	0.952
5:129760548:G:T	W112C	0.952
5:129764906:T:C	F139S	0.947
5:129748207:T:C	L6S	0.946
5:129760546:T:A	W112R	0.944
5:129760546:T:C	W112R	0.944
5:129764936:T:C	F149S	0.943
5:129764908:T:G	W140G	0.940
5:129764948:T:C	L153S	0.936
5:129748220:C:A	N10K	0.934
5:129748220:C:G	N10K	0.934
5:129748334:G:C	W48C	0.931
5:129748334:G:T	W48C	0.931
5:129764909:G:C	W140S	0.930
5:129748234:T:C	F15S	0.929
5:129748243:T:C	L18P	0.929
5:129748233:T:C	F15L	0.928
5:129748235:C:A	F15L	0.928
5:129748235:C:G	F15L	0.928
5:129748214:T:A	N8K	0.920

dbSNP variants (sampled 300 via entrez): RS1000071230 (5:129750580 A>G), RS1000080732 (5:129750274 G>A,C), RS1000096388 (5:129755767 T>C), RS1000117237 (5:129757347 A>C), RS1000189553 (5:129755746 T>C), RS1000633519 (5:129747617 C>A,T), RS1000698574 (5:129753968 T>C), RS1000713883 (5:129761416 G>A,T), RS1001166813 (5:129759698 C>A), RS1001586686 (5:129752937 A>T), RS1001601970 (5:129765515 T>G), RS1001719503 (5:129760011 A>C,G,T), RS1001815655 (5:129752402 A>T), RS1002099555 (5:129752678 A>G), RS1002169601 (5:129758107 A>G)

Disease associations

OMIM: gene MIM:620215 | disease phenotypes: MIM:620238

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive 120	Strong	Autosomal recessive

Mondo (1): hearing loss, autosomal recessive 120 (MONDO:0859374)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0003577	Congenital onset

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST009724_48	Vertical cup-disc ratio (multi-trait analysis)	8.000000e-10
GCST010701_92	Cortical surface area (MOSTest)	9.000000e-14
GCST010702_112	Subcortical volume (MOSTest)	1.000000e-09
GCST010703_249	Brain morphology (MOSTest)	2.000000e-14
GCST012227_187	Hip circumference adjusted for BMI	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Diethylhexyl Phthalate	decreases expression	1
Niclosamide	decreases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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