NBPF12

Summary

NBPF12 (NBPF member 12, HGNC:24297) is a protein-coding gene on chromosome 1q21.1, encoding NBPF family member NBPF12 (Q5TAG4). It is a selective cancer dependency (DepMap: 60.0% of cell lines).

This gene is a member of the neuroblastoma breakpoint family (NBPF) which consists of dozens of recently duplicated genes primarily located in segmental duplications on human chromosome 1. This gene family has experienced its greatest expansion within the human lineage and has expanded, to a lesser extent, among primates in general. Members of this gene family are characterized by tandemly repeated copies of DUF1220 protein domains. Gene copy number variations in the human chromosomal region 1q21.1, where most DUF1220 domains are located, have been implicated in a number of developmental and neurogenetic diseases such as microcephaly, macrocephaly, autism, schizophrenia, cognitive disability, congenital heart disease, neuroblastoma, and congenital kidney and urinary tract anomalies. Altered expression of some gene family members is associated with several types of cancer. This gene family contains numerous pseudogenes.

Source: NCBI Gene 149013 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 9 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 60.0% of screened cell lines
• MANE Select transcript: NM_001278141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24297
Approved symbol	NBPF12
Name	NBPF member 12
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	COAS1
Ensembl gene	ENSG00000268043
Ensembl biotype	protein_coding
OMIM	608607
Entrez	149013

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000617931, ENST00000698835, ENST00000698937, ENST00000909978, ENST00000939901

RefSeq mRNA: 1 — MANE Select: NM_001278141 NM_001278141

CCDS: CCDS72881

Canonical transcript exons

ENST00000698835 — 37 exons

Exon	Start	End
ENSE00001950169	146975677	146975891
ENSE00003461899	146968448	146968550
ENSE00003469404	146964893	146965104
ENSE00003491869	146985705	146985756
ENSE00003506221	146982928	146983091
ENSE00003513317	146966464	146966673
ENSE00003538544	146976929	146977001
ENSE00003569460	146963095	146963309
ENSE00003590339	146960109	146960318
ENSE00003595780	146987954	146988126
ENSE00003600318	146969382	146969596
ENSE00003600848	146986352	146986524
ENSE00003619851	146987234	146987285
ENSE00003631061	146988841	146988949
ENSE00003650109	146984134	146984185
ENSE00003669183	146962161	146962263
ENSE00003670915	146964357	146964429
ENSE00003692584	146984813	146984985
ENSE00003695573	146992712	146992884
ENSE00003696718	146991113	146991285
ENSE00003698741	146993599	146993707
ENSE00003701538	146991995	146992046
ENSE00003713183	146951348	146951489
ENSE00003718439	146977466	146977671
ENSE00003725774	146974739	146974841
ENSE00003738897	146971183	146971394
ENSE00003739012	146978959	146979010
ENSE00003741673	146970647	146970719
ENSE00003743058	146972751	146972960
ENSE00003747798	146959859	146960006
ENSE00003750589	146943291	146943562
ENSE00003753662	146989574	146989746
ENSE00003754077	146990466	146990517
ENSE00003967152	146938324	146939012
ENSE00003967154	146994332	146996198
ENSE00003974925	146949324	146949422
ENSE00003974928	146946555	146946607

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.04.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2417 / max 17.2921, expressed in 733 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201681	0.7883	498
4969	0.4535	257

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.04	gold quality
body of stomach	UBERON:0001161	91.04	gold quality
stomach	UBERON:0000945	89.30	gold quality
liver	UBERON:0002107	87.01	gold quality
right lobe of liver	UBERON:0001114	86.33	gold quality
ventricular zone	UBERON:0003053	86.25	gold quality
cortical plate	UBERON:0005343	85.68	gold quality
fundus of stomach	UBERON:0001160	85.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.15	gold quality
body of pancreas	UBERON:0001150	85.05	gold quality
tonsil	UBERON:0002372	85.04	gold quality
granulocyte	CL:0000094	85.03	gold quality
ganglionic eminence	UBERON:0004023	84.35	gold quality
bone marrow	UBERON:0002371	83.87	gold quality
pancreas	UBERON:0001264	83.49	gold quality
mucosa of stomach	UBERON:0001199	83.44	gold quality
bone marrow cell	CL:0002092	83.42	gold quality
primary visual cortex	UBERON:0002436	82.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.51	gold quality
cerebellar cortex	UBERON:0002129	82.39	gold quality
cerebellum	UBERON:0002037	82.38	gold quality
cerebellar hemisphere	UBERON:0002245	82.31	gold quality
superior frontal gyrus	UBERON:0002661	82.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.78	gold quality
left ovary	UBERON:0002119	81.77	gold quality
lower esophagus	UBERON:0013473	81.77	gold quality
ovary	UBERON:0000992	81.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting NBPF12, 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-4692	100.00	67.32	2066
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-329-5P	99.27	68.11	1597

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21; (COAS1, COAS2, COAS3) (PMID:11948409)

Cross-species orthologs

0 orthologs

Paralogs (14): NBPF3 (ENSG00000142794), NBPF20 (ENSG00000162825), NBPF6 (ENSG00000186086), NBPF4 (ENSG00000196427), NBPF1 (ENSG00000219481), NBPF11 (ENSG00000263956), NBPF15 (ENSG00000266338), NBPF9 (ENSG00000269713), NBPF8 (ENSG00000270231), NBPF14 (ENSG00000270629), (ENSG00000271254), NBPF19 (ENSG00000271383), NBPF10 (ENSG00000271425), NBPF26 (ENSG00000273136)

Protein

Protein identifiers

NBPF family member NBPF12 — Q5TAG4 (reviewed: Q5TAG4)

Alternative names: Chromosome 1 amplified sequence 1, Neuroblastoma breakpoint family member 12

All UniProt accessions (2): Q5TAG4, A0A8V8TNX8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed with highest levels in brain, ovary, mammary gland, skin and adipose tissue. Also expressed in testis. Detected in a number of tumors including osteosarcoma, mammary carcinoma and hepatocellular carcinoma.

Miscellaneous. Encoded by one of the numerous copies of NBPF genes clustered in the p36, p12 and q21 region of the chromosome 1.

Similarity. Belongs to the NBPF family.

RefSeq proteins (1): NP_001265070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010630	Olduvai_dom	Domain
IPR055306	NBPF	Family

Pfam: PF06758

UniProt features (29 total): domain 11, compositionally biased region 8, region of interest 6, coiled-coil region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TAG4-F1	45.84	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, chr1q21, CAVIN1_TARGET_GENES, E2F5_TARGET_GENES, HMG20B_TARGET_GENES, MEF2D_TARGET_GENES, ZBTB18_TARGET_GENES, ZFP91_TARGET_GENES, ZNF2_TARGET_GENES, ZNF524_TARGET_GENES, ZNF528_TARGET_GENES, ZNF592_TARGET_GENES, ZNF660_TARGET_GENES, ZSCAN30_TARGET_GENES, MIR3529_3P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NBPF12	PPIAL4E	A0A075B759	989
NBPF12	PPIAL4C	A0A0B4J2A2	988
NBPF12	PPIAL4G	P0DN37	986
NBPF12	PPIAL4A	Q9Y536	986
NBPF12	PPIAL4D	F5H284	482
NBPF12	NOTCH2NLB	P0DPK3	480
NBPF12	PPIA	P05092	464
NBPF12	ANKRD20A4P	Q4UJ75	448
NBPF12	HYDIN	Q4G0P3	379
NBPF12	ACP6	Q9NPH0	371
NBPF12	ADAM30	Q9UKF2	351
NBPF12	CYB561D1	Q8N8Q1	324
NBPF12	VHLL	Q6RSH7	321
NBPF12	PAIP2B	Q9ULR5	311
NBPF12	PPIL4	Q8WUA2	304

IntAct

3 interactions, top by confidence:

A	B	Type	Score
Tgfbr1	HSPA8	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0U1RQI7, A0A1D9BZF0, A6NJU9, A6NKU9, A6NNC1, A6QL64, A8MRT5, B2SU53, B4DH59, B5DUH6, C9JG80, E5RHQ5, F8W0I5, P01068, P02895, P06916, P07907, P0DKL2, P0DPF3, P0DRJ4, P13208, P14417, P32072, P83060, Q26755, Q3BBV0, Q3BBV2, Q4ZJY7, Q4ZJZ0, Q4ZJZ1, Q4ZJZ3, Q5TAG4, Q5TI25, Q6P3W6, Q6RY98, Q7T3L1, Q86SG3, Q86T75

Diamond homologs: A0A087WUL8, B4DH59, P0C2Y1, P0DPF2, P0DPF3, Q32LC2, Q3BBV0, Q3BBV2, Q5TAG4, Q5TI25, Q5VU43, Q5VWK0, Q6P3W6, Q86T75, Q86XG9, Q8N660, Q96M43, Q9H094, A0A096LNW5, A2RUV0, G3I6Z6, O35516, P0DPK3, P0DPK4, P10040, P21783, P46530, P46531, Q01705, Q04721, Q04756, Q07008, Q20911, Q7Z3S9, Q80YT7, Q99466, Q9QW30, Q9UM47, Q19UN5, Q8K389

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	2
Likely pathogenic	0
Uncertain significance	0
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
565165	GRCh37/hg19 1q21.1-21.2(chr1:145786289-147830830)x1	Pathogenic
625818	GRCh37/hg19 1q21.1-21.2(chr1:145740598-147825678)	Pathogenic

SpliceAI

4705 predictions. Top by Δscore:

Variant	Effect	Δscore
1:146960107:A:AG	acceptor_gain	1.0000
1:146960108:G:GA	acceptor_gain	1.0000
1:146960108:GTCCC:G	acceptor_gain	1.0000
1:146960319:G:GG	donor_gain	1.0000
1:146962159:A:AG	acceptor_gain	1.0000
1:146962160:G:GG	acceptor_gain	1.0000
1:146962160:GA:G	acceptor_gain	1.0000
1:146962251:C:G	donor_gain	1.0000
1:146962260:TCAG:T	donor_loss	1.0000
1:146962261:CAG:C	donor_loss	1.0000
1:146962262:AG:A	donor_loss	1.0000
1:146962263:GGTGA:G	donor_loss	1.0000
1:146962265:T:A	donor_loss	1.0000
1:146964352:TATAG:T	acceptor_loss	1.0000
1:146964353:ATAGA:A	acceptor_loss	1.0000
1:146964355:A:AG	acceptor_gain	1.0000
1:146964355:AG:A	acceptor_loss	1.0000
1:146964356:G:GC	acceptor_gain	1.0000
1:146964356:GA:G	acceptor_gain	1.0000
1:146964356:GAA:G	acceptor_gain	1.0000
1:146964356:GAAA:G	acceptor_gain	1.0000
1:146965083:G:GT	donor_gain	1.0000
1:146966462:A:AG	acceptor_gain	1.0000
1:146966463:G:GT	acceptor_gain	1.0000
1:146966463:GTC:G	acceptor_gain	1.0000
1:146966463:GTCC:G	acceptor_gain	1.0000
1:146966463:GTCCC:G	acceptor_gain	1.0000
1:146966674:G:GG	donor_gain	1.0000
1:146966700:A:T	donor_gain	1.0000
1:146966733:GAAAC:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1043477 (1:146994545 C>G,T), RS1043489 (1:146994714 G>A,T), RS1043491 (1:146994716 G>A,C,T), RS1043508 (1:146994816 G>A), RS1065120 (1:146995664 T>A,C), RS10900302 (1:146941420 A>G), RS111214369 (1:146987860 T>A,C), RS111240280 (1:146993038 C>A,G), RS111257006 (1:146995793 C>A,G,T), RS111318132 (1:146992983 A>C,G), RS111385707 (1:146988889 A>C), RS111714109 (1:146995889 C>A,T), RS111770433 (1:146994537 C>A,T), RS111962883 (1:146991942 T>C), RS112028663 (1:146993179 G>A,T)

Disease associations

OMIM: gene MIM:608607 | disease phenotypes: MIM:612475

GenCC curated gene-disease

Mondo (1): chromosome 1q21.1 duplication syndrome (MONDO:0012915)

Orphanet (1): 1q21.1 microduplication syndrome (Orphanet:250994)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567290	Chromosome 1q21.1 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Cadmium	increases abundance, increases expression	1
Pesticides	decreases expression	1
Rotenone	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight