NUTM2A

Summary

NUTM2A (NUT family member 2A, HGNC:23438) is a protein-coding gene on chromosome 10q23.2, encoding NUT family member 2A (Q8IVF1). It is a selective cancer dependency (DepMap: 22.4% of cell lines).

At a glance

• Clinical variants (ClinVar): 145 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 22.4% of screened cell lines
• MANE Select transcript: NM_001099338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23438
Approved symbol	NUTM2A
Name	NUT family member 2A
Location	10q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184923
Ensembl biotype	protein_coding
Entrez	728118

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000381689, ENST00000381707

RefSeq mRNA: 1 — MANE Select: NM_001099338 NM_001099338

CCDS: CCDS44452

Canonical transcript exons

ENST00000381707 — 7 exons

Exon	Start	End
ENSE00002441741	87230920	87231048
ENSE00002452281	87228263	87228962
ENSE00002471679	87233473	87233589
ENSE00002483461	87232603	87232985
ENSE00002498210	87232021	87232160
ENSE00002507730	87233923	87234978
ENSE00002723028	87225448	87226212

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 68.63.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	68.63	silver quality
apex of heart	UBERON:0002098	67.94	gold quality
prefrontal cortex	UBERON:0000451	66.47	gold quality
mucosa of stomach	UBERON:0001199	66.20	gold quality
colonic epithelium	UBERON:0000397	64.43	silver quality
right lung	UBERON:0002167	64.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.06	gold quality
heart left ventricle	UBERON:0002084	63.88	gold quality
right atrium auricular region	UBERON:0006631	63.23	gold quality
ventricular zone	UBERON:0003053	63.20	gold quality
granulocyte	CL:0000094	63.14	gold quality
frontal cortex	UBERON:0001870	62.83	gold quality
mucosa of transverse colon	UBERON:0004991	62.68	gold quality
cortical plate	UBERON:0005343	62.64	gold quality
gastrocnemius	UBERON:0001388	62.52	gold quality
heart	UBERON:0000948	62.20	gold quality
right uterine tube	UBERON:0001302	62.18	gold quality
muscle of leg	UBERON:0001383	62.06	gold quality
right coronary artery	UBERON:0001625	62.04	gold quality
fundus of stomach	UBERON:0001160	61.59	gold quality
right adrenal gland	UBERON:0001233	61.38	gold quality
Ammon’s horn	UBERON:0001954	61.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.01	gold quality
lower esophagus	UBERON:0013473	60.99	gold quality
body of stomach	UBERON:0001161	60.98	gold quality
placenta	UBERON:0001987	60.98	gold quality
cerebral cortex	UBERON:0000956	60.94	gold quality
right adrenal gland cortex	UBERON:0035827	60.85	gold quality
left adrenal gland	UBERON:0001234	60.79	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting NUTM2A, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-10392-3P	88.79	61.83	122

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of endometrial stromal sarcoma (ESS), which is associated with high-grade morphology and aggressive clinical behavior compared to JAZF1 ESS. (PMID:22456610)
• Case Report: genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. (PMID:28188754)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nutm2	ENSMUSG00000071909
rattus_norvegicus	Nutm2	ENSRNOG00000027311

Paralogs (6): NUTM2F (ENSG00000130950), NUTM1 (ENSG00000184507), NUTM2G (ENSG00000188152), NUTM2B (ENSG00000188199), NUTM2D (ENSG00000214562), NUTM2E (ENSG00000228570)

Protein

Protein identifiers

NUT family member 2A — Q8IVF1 (reviewed: Q8IVF1)

All UniProt accessions (1): Q8IVF1

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the NUT family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IVF1-1	1	yes
Q8IVF1-2	2

RefSeq proteins (1): NP_001092808* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024309	NUT_N	Domain
IPR024310	NUT	Family

Pfam: PF12881

UniProt features (14 total): region of interest 4, compositionally biased region 4, sequence conflict 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVF1-F1	47.48	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 6 (showing top): ROVERSI_GLIOMA_COPY_NUMBER_DN, chr10q23, MIR637, MIR4260, MANNO_MIDBRAIN_NEUROTYPES_HGABA, PULVER_FOREY_CELLCYCLE_PEAKING_G2

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUTM2A	YWHAE	P29360	768
NUTM2A	JAZF1	Q86VZ6	699
NUTM2A	ZC3H7B	Q9UGR2	682
NUTM2A	EZHIP	Q86X51	549
NUTM2A	PHF1	O43189	545
NUTM2A	MEAF6	Q9HAF1	528
NUTM2A	MBTD1	Q05BQ5	510
NUTM2A	ZC3H7A	Q8IWR0	489
NUTM2A	SUZ12	Q15022	479
NUTM2A	CCDC172	P0C7W6	419
NUTM2A	LEUTX	A8MZ59	419
NUTM2A	KRTAP10-6	P60371	418
NUTM2A	CCNB3	Q8WWL7	358
NUTM2A	ZNF730	Q6ZMV8	349
NUTM2A	DUX4L2	P0CJ85	322

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NUTM2A	actP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): NUTM2A (Affinity Capture-RNA), NUTM2A (Affinity Capture-MS), NUTM2A (Affinity Capture-MS), NUTM2A (Affinity Capture-MS), NUTM2A (Affinity Capture-MS)

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A1L443, A2IDD5, A5D7L8, A6NDY2, A6NIJ5, A6NNJ1, A6NNL0, A7E346, A8K0R7, A8MXJ8, A8MXZ1, B1AL46, B1ASB6, C9JSJ3, E9PGG2, O08574, P0C7V4, P0C7W8, P0C7X0, P0CG20, P0DV73, P0DV75, P0DV76, Q0VG99, Q0ZCJ7, Q149B8, Q2M3G4, Q3TQ03, Q3V0C3, Q4KLY2, Q5JXC2, Q5RCJ6, Q5SV97, Q5SW24, Q5VT03, Q5VZR2, Q6ZMY3

Diamond homologs: A1L443, A6NNL0, B1AL46, Q3V0C3, Q5VT03, Q5VZR2, Q86Y26, Q8BHP2, Q8IVF1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	140
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3244887	NC_000010.10:g.(?88514773)(89725229_?)del	Pathogenic

SpliceAI

1291 predictions. Top by Δscore:

Variant	Effect	Δscore
10:87230918:A:AG	acceptor_gain	1.0000
10:87230919:G:GA	acceptor_gain	1.0000
10:87230919:GC:G	acceptor_gain	1.0000
10:87230919:GCC:G	acceptor_gain	1.0000
10:87230919:GCCC:G	acceptor_gain	1.0000
10:87230919:GCCCA:G	acceptor_gain	1.0000
10:87231044:GAAAA:G	donor_gain	1.0000
10:87231045:AAAA:A	donor_gain	1.0000
10:87231046:AAA:A	donor_gain	1.0000
10:87231047:AA:A	donor_gain	1.0000
10:87231048:AG:A	donor_loss	1.0000
10:87231049:G:GG	donor_gain	1.0000
10:87232018:CAGGT:C	acceptor_loss	1.0000
10:87232019:AGGTT:A	acceptor_loss	1.0000
10:87232602:GT:G	acceptor_gain	1.0000
10:87232905:G:GT	donor_gain	1.0000
10:87233464:T:TA	acceptor_gain	1.0000
10:87233469:CCAG:C	acceptor_loss	1.0000
10:87233471:A:AG	acceptor_gain	1.0000
10:87233471:A:T	acceptor_loss	1.0000
10:87233471:AG:A	acceptor_gain	1.0000
10:87233471:AGGT:A	acceptor_gain	1.0000
10:87233471:AGGTG:A	acceptor_gain	1.0000
10:87233472:G:GT	acceptor_gain	1.0000
10:87233472:GG:G	acceptor_gain	1.0000
10:87233472:GGT:G	acceptor_gain	1.0000
10:87233472:GGTG:G	acceptor_gain	1.0000
10:87233472:GGTGG:G	acceptor_gain	1.0000
10:87233569:G:GT	donor_gain	1.0000
10:87233570:A:T	donor_gain	1.0000

AlphaMissense

5606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:87230998:G:C	W387C	0.992
10:87230998:G:T	W387C	0.992
10:87230996:T:A	W387R	0.991
10:87230996:T:C	W387R	0.991
10:87228955:T:C	F359L	0.990
10:87228957:C:A	F359L	0.990
10:87228957:C:G	F359L	0.990
10:87232022:T:C	F405L	0.989
10:87232024:C:A	F405L	0.989
10:87232024:C:G	F405L	0.989
10:87231029:T:C	F398L	0.987
10:87231031:C:A	F398L	0.987
10:87231031:C:G	F398L	0.987
10:87232031:T:C	F408L	0.986
10:87232033:T:A	F408L	0.986
10:87232033:T:G	F408L	0.986
10:87231021:G:C	R395P	0.982
10:87232023:T:C	F405S	0.982
10:87228886:T:A	W336R	0.979
10:87228886:T:C	W336R	0.979
10:87230997:G:C	W387S	0.979
10:87233497:T:C	F587L	0.975
10:87233499:C:A	F587L	0.975
10:87233499:C:G	F587L	0.975
10:87228877:T:C	F333L	0.973
10:87228879:C:A	F333L	0.973
10:87228879:C:G	F333L	0.973
10:87228952:T:C	C358R	0.973
10:87228888:G:C	W336C	0.972
10:87228888:G:T	W336C	0.972

dbSNP variants (sampled 300 via entrez): RS1002902706 (10:87229340 C>G), RS1003233145 (10:87235162 C>T), RS1005015428 (10:87229183 C>T), RS1005500198 (10:87224836 T>C), RS1009140376 (10:87223584 C>G,T), RS1009972363 (10:87223765 T>C), RS1011549405 (10:87233063 C>T), RS1011994987 (10:87229444 CA>C), RS1014968806 (10:87224849 C>T), RS1015385813 (10:87234483 G>A), RS1015454919 (10:87224230 C>G), RS1015726393 (10:87234918 G>A), RS1019170258 (10:87223911 G>A), RS1019242261 (10:87223618 G>A), RS1019500890 (10:87234366 G>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): PTEN hamartoma tumor syndrome (MONDO:0017623)

Orphanet (1): PTEN hamartoma tumor syndrome (Orphanet:306498)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
ferrous chloride	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Cisplatin	decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04094675	PHASE2	COMPLETED	Sirolimus for Cowden Syndrome With Colon Polyposis
NCT07218575	PHASE2/PHASE3	NOT_YET_RECRUITING	Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NCT02991807	PHASE1/PHASE2	COMPLETED	RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome
NCT06080165	PHASE1/PHASE2	WITHDRAWN	Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
NCT02461446	Not specified	RECRUITING	Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03630523	Not specified	UNKNOWN	Response of Immune System to Flu Vaccination in PHTS
NCT05671107	Not specified	COMPLETED	Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients
NCT06462430	Not specified	RECRUITING	PTEN Hamartoma Tumor Syndrome Pediatric Patient Registry