NBPF6

Summary

NBPF6 (NBPF member 6, HGNC:31988) is a protein-coding gene on chromosome 1p13.3, encoding NBPF family member NBPF6 (Q5VWK0).

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. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 653149 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_001143988

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31988
Approved symbol	NBPF6
Name	NBPF member 6
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186086
Ensembl biotype	protein_coding
OMIM	613996
Entrez	653149

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000370040, ENST00000495380, ENST00000531446

RefSeq mRNA: 2 — MANE Select: NM_001143988 NM_001143987, NM_001143988

CCDS: CCDS44184

Canonical transcript exons

ENST00000495380 — 15 exons

Exon	Start	End
ENSE00001600935	108453181	108453395
ENSE00001658235	108454439	108454517
ENSE00001752745	108452190	108452289
ENSE00001805673	108450567	108450779
ENSE00002194019	108450343	108450464
ENSE00003718394	108467451	108467665
ENSE00003721351	108459058	108459109
ENSE00003726919	108465188	108465424
ENSE00003731993	108470597	108471920
ENSE00003732117	108461133	108461184
ENSE00003739926	108457007	108457058
ENSE00003746343	108455386	108455597
ENSE00003748451	108459933	108460102
ENSE00003749312	108457936	108458075
ENSE00003754657	108461916	108462088

Expression profiles

Bgee: expression breadth broad, 31 present calls, max score 56.44.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
testis	UBERON:0000473	56.44	gold quality
left testis	UBERON:0004533	55.96	gold quality
right testis	UBERON:0004534	54.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	51.33	gold quality
placenta	UBERON:0001987	50.96	gold quality
small intestine	UBERON:0002108	50.14	gold quality
adenohypophysis	UBERON:0002196	47.22	gold quality
pituitary gland	UBERON:0000007	47.03	gold quality
putamen	UBERON:0001874	46.82	gold quality
duodenum	UBERON:0002114	45.30	gold quality
rectum	UBERON:0001052	45.02	gold quality
tibial artery	UBERON:0007610	43.35	gold quality
popliteal artery	UBERON:0002250	43.34	gold quality
colonic epithelium	UBERON:0000397	41.59	gold quality
caudate nucleus	UBERON:0001873	41.39	gold quality
right coronary artery	UBERON:0001625	40.92	silver quality
gall bladder	UBERON:0002110	39.50	silver quality
right adrenal gland cortex	UBERON:0035827	38.46	silver quality
lymph node	UBERON:0000029	37.40	gold quality
tonsil	UBERON:0002372	37.06	silver quality
monocyte	CL:0000576	37.00	silver quality
left coronary artery	UBERON:0001626	36.92	gold quality
leukocyte	CL:0000738	36.75	silver quality
prefrontal cortex	UBERON:0000451	36.67	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
mucosa of transverse colon	UBERON:0004991	36.11	gold quality
intestine	UBERON:0000160	35.67	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (14): NBPF3 (ENSG00000142794), NBPF20 (ENSG00000162825), NBPF4 (ENSG00000196427), NBPF1 (ENSG00000219481), NBPF11 (ENSG00000263956), NBPF15 (ENSG00000266338), NBPF12 (ENSG00000268043), NBPF9 (ENSG00000269713), NBPF8 (ENSG00000270231), NBPF14 (ENSG00000270629), (ENSG00000271254), NBPF19 (ENSG00000271383), NBPF10 (ENSG00000271425), NBPF26 (ENSG00000273136)

Protein

Protein identifiers

NBPF family member NBPF6 — Q5VWK0 (reviewed: Q5VWK0)

Alternative names: Neuroblastoma breakpoint family member 6

All UniProt accessions (2): A0A0B4J227, Q5VWK0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VWK0-1	1	yes
Q5VWK0-2	2

RefSeq proteins (2): NP_001137459, NP_001137460* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010630	Olduvai_dom	Domain
IPR055306	NBPF	Family

Pfam: PF06758

UniProt features (14 total): compositionally biased region 5, domain 3, region of interest 2, coiled-coil region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VWK0-F1	51.18	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 1 (showing top): chr1p13

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

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NBPF6	PROX2	Q3B8N5	447
NBPF6	TMTC2	Q8N394	350
NBPF6	EXOC3L2	Q2M3D2	344
NBPF6	USP42	Q9H9J4	333
NBPF6	PLEKHM3	Q6ZWE6	326
NBPF6	FPGT	O14772	324
NBPF6	MINPP1	Q9UNW1	323
NBPF6	B3GLCT	Q6Y288	319
NBPF6	SLC25A24	Q6NUK1	303
NBPF6	BRINP1	O60477	292
NBPF6	NOTCH2NLB	P0DPK3	290
NBPF6	BEND3	Q5T5X7	289
NBPF6	PSRC1	Q6PGN9	267
NBPF6	MARK4	Q96L34	263
NBPF6	SEMA6D	Q8NFY4	233

IntAct

0 interactions, top by confidence:

BioGRID (5): NBPF6 (Affinity Capture-RNA), NBPF6 (Two-hybrid), NBPF6 (Two-hybrid), NBPF6 (Two-hybrid), AQP1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2303 predictions. Top by Δscore:

Variant	Effect	Δscore
1:108450465:G:GG	donor_gain	1.0000
1:108450775:ATACA:A	donor_gain	1.0000
1:108450776:TACA:T	donor_gain	1.0000
1:108450778:CA:C	donor_gain	1.0000
1:108450779:AG:A	donor_loss	1.0000
1:108450780:G:GG	donor_gain	1.0000
1:108450780:G:T	donor_loss	1.0000
1:108450781:T:A	donor_loss	1.0000
1:108452188:A:AG	acceptor_gain	1.0000
1:108452189:G:GA	acceptor_gain	1.0000
1:108452189:GA:G	acceptor_gain	1.0000
1:108452189:GAGT:G	acceptor_gain	1.0000
1:108452273:C:T	donor_gain	1.0000
1:108452287:CAGG:C	donor_loss	1.0000
1:108452289:GGTG:G	donor_loss	1.0000
1:108452291:T:A	donor_loss	1.0000
1:108453180:GGCA:G	acceptor_gain	1.0000
1:108454435:GCAGA:G	acceptor_loss	1.0000
1:108454436:CA:C	acceptor_loss	1.0000
1:108454437:A:AC	acceptor_loss	1.0000
1:108454437:A:AG	acceptor_gain	1.0000
1:108454438:G:GC	acceptor_gain	1.0000
1:108454438:GA:G	acceptor_gain	1.0000
1:108454438:GAA:G	acceptor_gain	1.0000
1:108454438:GAAA:G	acceptor_gain	1.0000
1:108454438:GAAAA:G	acceptor_gain	1.0000
1:108454483:G:GT	donor_gain	1.0000
1:108454501:G:GT	donor_gain	1.0000
1:108454516:AG:A	donor_loss	1.0000
1:108454517:GGTAA:G	donor_loss	1.0000

AlphaMissense

4212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:108450740:G:C	A47P	0.974
1:108450768:T:C	L56P	0.970
1:108453219:T:C	L106P	0.967
1:108450758:G:C	A53P	0.965
1:108450756:T:C	L52P	0.956
1:108453209:G:C	A103P	0.948
1:108450725:T:C	F42L	0.946
1:108450727:C:A	F42L	0.946
1:108450727:C:G	F42L	0.946
1:108453270:T:C	L123P	0.937
1:108450729:T:C	L43P	0.935
1:108453248:G:T	G116W	0.935
1:108450704:T:C	F35L	0.934
1:108450706:C:A	F35L	0.934
1:108450706:C:G	F35L	0.934
1:108453365:G:C	A155P	0.934
1:108450714:T:C	L38P	0.933
1:108453231:G:C	R110P	0.931
1:108450746:G:C	A49P	0.930
1:108453353:G:A	G151R	0.924
1:108453353:G:C	G151R	0.924
1:108450738:A:C	Q46P	0.923
1:108450765:A:C	Q55P	0.922
1:108450684:T:C	L28P	0.918
1:108453375:T:C	L158P	0.918
1:108453248:G:A	G116R	0.915
1:108453248:G:C	G116R	0.915
1:108453228:T:C	L109S	0.914
1:108453345:T:C	L148P	0.910
1:108450708:G:C	R36P	0.909

dbSNP variants (sampled 300 via entrez): RS1000848170 (1:108471508 A>G,T), RS1000983412 (1:108471320 G>A), RS1001100531 (1:108436310 T>C,G), RS1001526919 (1:108438012 A>T), RS1001772989 (1:108464554 T>C), RS1001902875 (1:108222483 T>G), RS1001914967 (1:108472277 CTA>C), RS1002127969 (1:108448548 C>T), RS1002500246 (1:108447746 C>A,T), RS1002720744 (1:108468964 C>T), RS1002800800 (1:108469321 T>G), RS1003598444 (1:108425556 A>C,G), RS1004991481 (1:108460855 G>T), RS1005098118 (1:108459438 T>C), RS1005309929 (1:108429599 G>A,C)

Disease associations

OMIM: gene MIM:613996 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
Cadmium	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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