NBPF4

Summary

NBPF4 (NBPF member 4, HGNC:26550) is a protein-coding gene on chromosome 1p13.3, encoding NBPF family member NBPF4 (Q96M43).

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 148545 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001143989

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26550
Approved symbol	NBPF4
Name	NBPF member 4
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32833
Ensembl gene	ENSG00000196427
Ensembl biotype	protein_coding
OMIM	613994
Entrez	148545

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000415641, ENST00000613157

RefSeq mRNA: 1 — MANE Select: NM_001143989 NM_001143989

CCDS: CCDS44182

Canonical transcript exons

ENST00000415641 — 15 exons

Exon	Start	End
ENSE00001626564	108242074	108242173
ENSE00001697801	108240950	108241164
ENSE00001700362	108239828	108239906
ENSE00001769215	108243899	108244076
ENSE00001782605	108222464	108223746
ENSE00003485351	108232256	108232428
ENSE00003489766	108237287	108237338
ENSE00003524253	108226679	108226893
ENSE00003539942	108243584	108243796
ENSE00003577472	108234242	108234411
ENSE00003592514	108233160	108233211
ENSE00003604334	108228920	108229156
ENSE00003610688	108238748	108238959
ENSE00003616007	108236270	108236409
ENSE00003676282	108235236	108235287

Expression profiles

Bgee: expression breadth broad, 58 present calls, max score 88.26.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	88.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.65	silver quality
right testis	UBERON:0004534	62.09	gold quality
tibia	UBERON:0000979	61.03	silver quality
left testis	UBERON:0004533	61.01	gold quality
testis	UBERON:0000473	60.59	gold quality
palpebral conjunctiva	UBERON:0001812	59.94	silver quality
myocardium	UBERON:0002349	59.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	55.89	gold quality
adult organism	UBERON:0007023	55.56	silver quality
heart right ventricle	UBERON:0002080	55.55	gold quality
nasal cavity epithelium	UBERON:0005384	55.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	54.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	54.28	gold quality
small intestine	UBERON:0002108	53.90	gold quality
biceps brachii	UBERON:0001507	53.41	gold quality
jejunal mucosa	UBERON:0000399	53.12	gold quality
placenta	UBERON:0001987	50.52	gold quality
vastus lateralis	UBERON:0001379	49.88	gold quality
rectum	UBERON:0001052	49.74	gold quality
quadriceps femoris	UBERON:0001377	49.66	gold quality
seminal vesicle	UBERON:0000998	49.23	gold quality
tendon of biceps brachii	UBERON:0008188	48.18	gold quality
adenohypophysis	UBERON:0002196	48.03	gold quality
pituitary gland	UBERON:0000007	47.60	gold quality
mammalian vulva	UBERON:0000997	47.30	gold quality
jejunum	UBERON:0002115	47.19	gold quality
amniotic fluid	UBERON:0000173	46.67	gold quality
lower lobe of lung	UBERON:0008949	46.10	silver quality
putamen	UBERON:0001874	45.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2

Cross-species orthologs

0 orthologs

Paralogs (14): NBPF3 (ENSG00000142794), NBPF20 (ENSG00000162825), NBPF6 (ENSG00000186086), 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 NBPF4 — Q96M43 (reviewed: Q96M43)

Alternative names: Neuroblastoma breakpoint family member 4

All UniProt accessions (2): A0A087WVM6, Q96M43

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in testis.

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_001137461* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010630	Olduvai_dom	Domain
IPR055306	NBPF	Family

Pfam: PF06758

UniProt features (13 total): compositionally biased region 5, domain 3, region of interest 2, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96M43-F1	50.31	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 10 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR1285_3P, MIR5189_5P, MIR6515_5P, GSE13485_DAY1_VS_DAY7_YF17D_VACCINE_PBMC_UP, GSE25087_TREG_VS_TCONV_ADULT_DN, chr1p13, GSE30971_2H_VS_4H_LPS_STIM_MACROPHAGE_WBP7_HET_UP, GSE35543_IN_VIVO_NTREG_VS_IN_VITRO_ITREG_DN

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
NBPF4	EVPLL	A8MZ36	533
NBPF4	PRR20A	P86496	507
NBPF4	LRRC37A	A6NMS7	477
NBPF4	NOTCH2NLB	P0DPK3	443
NBPF4	CLCC1	Q96S66	397
NBPF4	TPTE	P56180	378
NBPF4	CLDN24	A6NM45	376
NBPF4	XAGE2	Q96GT9	372
NBPF4	NPIPA5	E9PKD4	360
NBPF4	NPIPB11	E5RHQ5	358
NBPF4	GPSM2	P81274	357
NBPF4	NPIPA3	F8WFD2	356
NBPF4	LRRC37A3	O60309	325
NBPF4	PDXDC1	Q6P996	322
NBPF4	KIAA0319L	Q8IZA0	317

IntAct

0 interactions, top by confidence:

BioGRID (2): NBPF4 (Affinity Capture-MS), NBPF4 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2339 predictions. Top by Δscore:

Variant	Effect	Δscore
1:108232248:GTACT:G	donor_loss	1.0000
1:108232250:ACTC:A	donor_loss	1.0000
1:108232252:TCA:T	donor_loss	1.0000
1:108232253:CACA:C	donor_loss	1.0000
1:108232254:A:AC	donor_gain	1.0000
1:108232255:C:CA	donor_gain	1.0000
1:108232255:C:G	donor_loss	1.0000
1:108232255:CAGG:C	donor_gain	1.0000
1:108232264:T:TA	donor_gain	1.0000
1:108232429:C:CC	acceptor_gain	1.0000
1:108232429:C:CG	acceptor_loss	1.0000
1:108234234:GTACT:G	donor_loss	1.0000
1:108234235:TACT:T	donor_loss	1.0000
1:108234236:ACTC:A	donor_loss	1.0000
1:108234238:TCA:T	donor_loss	1.0000
1:108234239:CA:C	donor_loss	1.0000
1:108234240:A:AC	donor_gain	1.0000
1:108234240:ACTG:A	donor_loss	1.0000
1:108234241:C:CC	donor_gain	1.0000
1:108236326:T:TA	donor_gain	1.0000
1:108237217:T:TA	donor_gain	1.0000
1:108238970:C:CT	acceptor_gain	1.0000
1:108238971:A:T	acceptor_gain	1.0000
1:108239826:A:C	donor_loss	1.0000
1:108239827:C:G	donor_loss	1.0000
1:108239843:T:TA	donor_gain	1.0000
1:108239861:T:TA	donor_gain	1.0000
1:108239902:ATTTT:A	acceptor_gain	1.0000
1:108239903:TTTT:T	acceptor_gain	1.0000
1:108239904:TTT:T	acceptor_gain	1.0000

AlphaMissense

4207 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:108241126:A:G	L106P	0.977
1:108243623:C:G	A47P	0.976
1:108243595:A:G	L56P	0.972
1:108243605:C:G	A53P	0.972
1:108243636:G:C	F42L	0.970
1:108243636:G:T	F42L	0.970
1:108243638:A:G	F42L	0.970
1:108243607:A:G	L52P	0.961
1:108243617:C:G	A49P	0.959
1:108241136:C:G	A103P	0.956
1:108243649:A:G	L38P	0.956
1:108243657:G:C	F35L	0.953
1:108243657:G:T	F35L	0.953
1:108243659:A:G	F35L	0.953
1:108240980:C:G	A155P	0.949
1:108243679:A:G	L28P	0.948
1:108243625:T:G	Q46P	0.945
1:108243634:A:G	L43P	0.935
1:108243598:T:G	Q55P	0.929
1:108241114:C:G	R110P	0.927
1:108243691:A:G	L24S	0.927
1:108241117:A:G	L109S	0.925
1:108243655:C:G	R36P	0.924
1:108240992:C:G	G151R	0.923
1:108240992:C:T	G151R	0.923
1:108241147:A:T	V99D	0.923
1:108241075:A:G	L123P	0.920
1:108243637:A:G	F42S	0.920
1:108243604:G:T	A53D	0.909
1:108243645:T:A	K39N	0.908

dbSNP variants (sampled 300 via entrez): RS1000115496 (1:108235943 G>T), RS1000529647 (1:108241815 T>C), RS1001557697 (1:108223556 G>C,T), RS1001902875 (1:108222483 T>G), RS1002467002 (1:108250360 G>A), RS1002659846 (1:108226484 G>A), RS1002865647 (1:108247697 A>G), RS1003017442 (1:108226061 C>G,T), RS1003074218 (1:108264373 G>A), RS1003083884 (1:108266036 TATA>T), RS1003411560 (1:108257281 T>C), RS1003873775 (1:108257960 G>A), RS1003973200 (1:108257229 G>A), RS1004086131 (1:108256180 T>C), RS1005251577 (1:108223490 C>T)

Disease associations

OMIM: gene MIM:613994 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	affects binding, decreases reaction	1
Cadmium	decreases expression	1
Estradiol	increases expression, increases reaction	1
Cyclosporine	increases methylation	1

Clinical trials (associated diseases)

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