PROB1

Summary

PROB1 (proline rich basic protein 1, HGNC:41906) is a protein-coding gene on chromosome 5q31.2, encoding Proline-rich basic protein 1 (E7EW31).

Located in nucleoplasm.

Source: NCBI Gene 389333 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 113 total
• MANE Select transcript: NM_001161546

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:41906
Approved symbol	PROB1
Name	proline rich basic protein 1
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000228672
Ensembl biotype	protein_coding
Entrez	389333

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000434752

RefSeq mRNA: 1 — MANE Select: NM_001161546 NM_001161546

CCDS: CCDS54909

Canonical transcript exons

ENST00000434752 — 1 exons

Exon	Start	End
ENSE00001788179	139390592	139395104

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 98.35.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9639 / max 51.6302, expressed in 387 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63750	0.6724	299
63751	0.1897	83
63748	0.0920	29
63749	0.0098	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	98.35	silver quality
gastrocnemius	UBERON:0001388	93.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.82	gold quality
muscle of leg	UBERON:0001383	92.17	gold quality
skeletal muscle tissue	UBERON:0001134	92.05	gold quality
apex of heart	UBERON:0002098	91.91	gold quality
thymus	UBERON:0002370	90.15	gold quality
heart left ventricle	UBERON:0002084	88.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.45	gold quality
heart	UBERON:0000948	82.20	gold quality
muscle tissue	UBERON:0002385	81.85	gold quality
right atrium auricular region	UBERON:0006631	81.17	gold quality
left adrenal gland	UBERON:0001234	73.80	gold quality
left adrenal gland cortex	UBERON:0035825	73.52	gold quality
right adrenal gland	UBERON:0001233	73.17	gold quality
adrenal gland	UBERON:0002369	72.55	gold quality
right adrenal gland cortex	UBERON:0035827	72.51	gold quality
stromal cell of endometrium	CL:0002255	70.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.53	gold quality
lower esophagus	UBERON:0013473	70.43	gold quality
right uterine tube	UBERON:0001302	70.17	gold quality
mucosa of transverse colon	UBERON:0004991	69.55	gold quality
prostate gland	UBERON:0002367	68.02	gold quality
adrenal tissue	UBERON:0018303	67.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	67.75	gold quality
cerebellar vermis	UBERON:0004720	67.71	gold quality
adenohypophysis	UBERON:0002196	66.41	gold quality
pituitary gland	UBERON:0000007	66.30	gold quality
amygdala	UBERON:0001876	65.76	gold quality
temporal lobe	UBERON:0001871	65.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.77

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Segregation analysis revealed that variants c.475T>G in SKP1, c.671G>A in PROB1, and c.527G>A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G>A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied Keratoconus family (PMID:27703147)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prob1	ENSMUSG00000073600
rattus_norvegicus	Prob1	ENSRNOG00000039596

Protein

Protein identifiers

Proline-rich basic protein 1 — E7EW31 (reviewed: E7EW31)

All UniProt accessions (1): E7EW31

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (1): NP_001155018* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027838	DUF4585	Domain
IPR052303	CEFIP	Family

Pfam: PF15232

UniProt features (25 total): compositionally biased region 16, region of interest 7, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-E7EW31-F1	44.63	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): chr5q31, FOURATI_BLOOD_TWINRIX_AGE_25_83YO_RESPONDERS_VS_POOR_RESPONDERS_0DY_DN, HARALAMBIEVA_PBMC_M_M_R_II_AGE_11_22YO_VACCINATED_VS_UNVACCINATED_7YR_UP, GENES_CORRELATED_WITH_MYC_DELETION, GSE8835_HEALTHY_VS_CLL_CD8_TCELL_UP, GSE2585_CD80_HIGH_VS_LOW_MTEC_UP, GSE8921_3H_VS_24H_TLR1_2_STIM_MONOCYTE_DN, GSE7831_1H_VS_4H_INFLUENZA_STIM_PDC_DN, GSE19888_ADENOSINE_A3R_INH_VS_INH_PRETREAT_AND_ACT_WITH_TCELL_MEMBRANES_MAST_CELL_DN, GSE24210_TCONV_VS_TREG_UP, GSE24972_WT_VS_IRF8_KO_MARGINAL_ZONE_SPLEEN_BCELL_DN, GSE36078_UNTREATED_VS_AD5_T425A_HEXON_INF_IL1R_KO_MOUSE_LUNG_DC_UP, GSE11961_MARGINAL_ZONE_BCELL_VS_GERMINAL_CENTER_BCELL_DAY7_DN, GSE43863_TH1_VS_TFH_EFFECTOR_CD4_TCELL_UP, GSE46606_IRF4MID_VS_WT_CD40L_IL2_IL5_DAY1_STIMULATED_BCELL_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROB1	SMIM33	A0A1B0GW64	571
PROB1	SPATA24	Q86W54	540
PROB1	JADE2	Q9NQC1	469
PROB1	PLEKHH3	Q7Z736	458
PROB1	NAGS	Q8N159	412
PROB1	ECSCR	Q19T08	403
PROB1	PHF23	Q9BUL5	401
PROB1	DNAJC18	Q9H819	395
PROB1	DRAM1	Q8N682	352
PROB1	DENND5B	Q6ZUT9	334
PROB1	NTN5	Q8WTR8	307
PROB1	PRDM7	Q9NQW5	305
PROB1	CYYR1	Q96J86	300
PROB1	VWA7	Q9Y334	297
PROB1	FAM171A1	Q5VUB5	297

IntAct

0 interactions, top by confidence:

BioGRID (2): PROB1 (Affinity Capture-MS), PROB1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	105
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

35 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139393028:T:TG	acceptor_gain	0.6900
5:139393029:T:A	acceptor_gain	0.6800
5:139391847:T:TA	donor_gain	0.5200
5:139393030:G:GA	acceptor_gain	0.4400
5:139393031:A:AA	acceptor_gain	0.4400
5:139393027:CTTGA:C	acceptor_gain	0.3900
5:139393032:T:A	acceptor_gain	0.3900
5:139393045:G:GT	acceptor_gain	0.3200
5:139393046:T:TT	acceptor_gain	0.3200
5:139393022:AAAT:A	acceptor_gain	0.3100
5:139390827:C:A	acceptor_gain	0.3000
5:139390757:C:CT	acceptor_gain	0.2800
5:139391816:A:C	donor_gain	0.2800
5:139393181:G:C	donor_gain	0.2700
5:139394197:AG:A	donor_gain	0.2700
5:139393023:AAT:A	acceptor_gain	0.2600
5:139393026:CCT:C	acceptor_gain	0.2600
5:139393028:T:C	acceptor_gain	0.2500
5:139393188:TC:T	donor_gain	0.2500
5:139394936:T:TA	donor_gain	0.2400
5:139390825:TCCC:T	acceptor_gain	0.2300
5:139390826:CCCC:C	acceptor_gain	0.2300
5:139393021:AAAAT:A	acceptor_gain	0.2300
5:139393024:AT:A	acceptor_gain	0.2300
5:139393952:CA:C	donor_gain	0.2300
5:139394948:T:TA	donor_gain	0.2300
5:139393038:C:A	acceptor_gain	0.2200
5:139393144:AGAG:A	donor_gain	0.2200
5:139391815:A:AC	donor_gain	0.2100
5:139393025:T:A	acceptor_gain	0.2100

AlphaMissense

6376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139394461:C:A	K207N	0.992
5:139394461:C:G	K207N	0.992
5:139392362:T:C	D907G	0.991
5:139394460:G:T	R208S	0.987
5:139392408:A:C	Y892D	0.985
5:139394065:A:C	S339R	0.985
5:139394065:A:T	S339R	0.985
5:139394067:T:G	S339R	0.985
5:139394581:C:A	W167C	0.985
5:139394581:C:G	W167C	0.985
5:139392434:A:G	L883S	0.984
5:139393186:C:A	K632N	0.983
5:139393186:C:G	K632N	0.983
5:139394737:G:C	F115L	0.982
5:139394737:G:T	F115L	0.982
5:139394739:A:G	F115L	0.982
5:139394059:G:C	S341R	0.980
5:139394059:G:T	S341R	0.980
5:139394061:T:G	S341R	0.980
5:139392345:A:C	Y913D	0.979
5:139392350:C:A	G911V	0.979
5:139392368:A:G	L905P	0.979
5:139392364:G:C	F906L	0.978
5:139392364:G:T	F906L	0.978
5:139392366:A:G	F906L	0.978
5:139392428:T:C	D885G	0.977
5:139394053:G:C	F343L	0.977
5:139394053:G:T	F343L	0.977
5:139394055:A:G	F343L	0.977
5:139394583:A:G	W167R	0.977

dbSNP variants (sampled 300 via entrez): RS1000037209 (5:139395931 A>G), RS1000257218 (5:139393599 T>G), RS1000348803 (5:139393322 G>A,T), RS1000518419 (5:139394934 C>T), RS1000591429 (5:139394856 G>A,C), RS1000686286 (5:139394636 G>A), RS1001114950 (5:139393638 G>C,T), RS1001231277 (5:139394346 C>T), RS1001568333 (5:139392929 C>T), RS1001682220 (5:139394604 C>T), RS1001898730 (5:139394320 C>G,T), RS1001914949 (5:139394060 C>A,G), RS1002575849 (5:139391629 G>A), RS1003236811 (5:139392040 C>A,G), RS1003698597 (5:139392292 G>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005951_151	Body mass index	6.000000e-07
GCST010725_68	Malaria	4.000000e-07
GCST010725_7	Malaria	2.000000e-06
GCST010796_3063	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3064	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_3065	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-14
GCST010796_3066	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-14
GCST012101_11	Hypertrophic cardiomyopathy	6.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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