USHBP1

Summary

USHBP1 (USH1 protein network component harmonin binding protein 1, HGNC:24058) is a protein-coding gene on chromosome 19p13.11, encoding Harmonin-binding protein USHBP1 (Q8N6Y0).

Enables PDZ domain binding activity.

Source: NCBI Gene 83878 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 144 total
• MANE Select transcript: NM_031941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24058
Approved symbol	USHBP1
Name	USH1 protein network component harmonin binding protein 1
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	MCC2, AIEBP, FLJ38709
Ensembl gene	ENSG00000130307
Ensembl biotype	protein_coding
OMIM	611810
Entrez	83878

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000252597, ENST00000324554, ENST00000431146, ENST00000594190, ENST00000595993, ENST00000596436, ENST00000597928, ENST00000598309, ENST00000598570, ENST00000600286, ENST00000881047, ENST00000881048, ENST00000965831

RefSeq mRNA: 3 — MANE Select: NM_031941 NM_001297703, NM_001321417, NM_031941

CCDS: CCDS12353, CCDS77256

Canonical transcript exons

ENST00000252597 — 13 exons

Exon	Start	End
ENSE00000895475	17262552	17262990
ENSE00003048589	17264671	17264745
ENSE00003143629	17249171	17250414
ENSE00003540814	17258212	17258385
ENSE00003557108	17259289	17259429
ENSE00003591104	17259897	17260022
ENSE00003594303	17251911	17252017
ENSE00003622312	17264002	17264150
ENSE00003629062	17259596	17259732
ENSE00003633357	17251582	17251704
ENSE00003633360	17264246	17264347
ENSE00003675306	17255385	17255606
ENSE00003675641	17256471	17256720

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 92.32.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1417 / max 68.5114, expressed in 343 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179848	1.0320	331
179847	0.1097	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.32	gold quality
sural nerve	UBERON:0015488	85.56	gold quality
right lung	UBERON:0002167	84.03	gold quality
heart left ventricle	UBERON:0002084	83.54	gold quality
cardiac ventricle	UBERON:0002082	82.96	gold quality
tendon of biceps brachii	UBERON:0008188	81.92	gold quality
omental fat pad	UBERON:0010414	81.77	gold quality
peritoneum	UBERON:0002358	81.70	gold quality
upper lobe of left lung	UBERON:0008952	81.21	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.52	gold quality
buccal mucosa cell	CL:0002336	80.24	silver quality
body of uterus	UBERON:0009853	79.00	gold quality
heart	UBERON:0000948	78.67	gold quality
upper lobe of lung	UBERON:0008948	78.55	gold quality
right lobe of thyroid gland	UBERON:0001119	78.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.38	gold quality
left ventricle myocardium	UBERON:0006566	78.22	gold quality
mucosa of stomach	UBERON:0001199	78.11	gold quality
adipose tissue	UBERON:0001013	78.01	gold quality
metanephros cortex	UBERON:0010533	77.42	gold quality
right atrium auricular region	UBERON:0006631	77.36	gold quality
cardiac atrium	UBERON:0002081	77.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.74	silver quality
left lobe of thyroid gland	UBERON:0001120	76.43	gold quality
gastrocnemius	UBERON:0001388	76.33	gold quality
muscle of leg	UBERON:0001383	76.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.20	gold quality
lower esophagus	UBERON:0013473	76.15	gold quality
thyroid gland	UBERON:0002046	75.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52
E-GEOD-106540	no	59.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting USHBP1, 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-198	98.70	67.32	920
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-668-3P	96.18	65.80	673

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ushbp1	ENSDARG00000089071
mus_musculus	Ushbp1	ENSMUSG00000034911
rattus_norvegicus	Ushbp1	ENSRNOG00000023485
drosophila_melanogaster	CG34404	FBGN0085433

Paralogs (1): MCC (ENSG00000171444)

Protein

Protein identifiers

Harmonin-binding protein USHBP1 — Q8N6Y0 (reviewed: Q8N6Y0)

Alternative names: AIE-75-binding protein, Mutated in colon cancer protein 2, Usher syndrome type-1C protein-binding protein 1

All UniProt accessions (5): Q8N6Y0, G8JLM4, M0R172, M0R3B1, Q8N8Y1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts via its C-terminus with the first PDZ domain of USH1C.

Tissue specificity. Highest level of expression in heart, and moderate to low expression in skeletal muscle, kidney, liver, small intestine, placenta and lung.

Miscellaneous. Due to the retention of an intron in the cDNA leading to a prematurate stop codon.

Similarity. Belongs to the MCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N6Y0-1	1	yes
Q8N6Y0-2	2

RefSeq proteins (3): NP_001284632, NP_001308346, NP_114147* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019536	USHBP1_PDZ-bd	Domain
IPR040171	USBP1-like	Family

Pfam: PF10506

UniProt features (23 total): sequence conflict 6, region of interest 5, coiled-coil region 4, compositionally biased region 3, sequence variant 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6Y0-F1	69.48	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): MARTINEZ_RB1_TARGETS_DN, NIKOLSKY_BREAST_CANCER_19P13_AMPLICON, RYTTCCTG_ETS2_B, MODULE_397, MARTINEZ_RB1_AND_TP53_TARGETS_UP, chr19p13, IGLV5_37_TARGET_GENES, NFKBIA_TARGET_GENES, TFEB_TARGET_GENES, ZNF768_TARGET_GENES, ZSCAN31_TARGET_GENES, GSE10147_IL3_VS_IL3_AND_HIVP17_STIM_PDC_DN, MODULE_486, GSE10422_WT_VS_BAFF_TRANSGENIC_LN_BCELL_DN, GSE17721_CTRL_VS_LPS_4H_BMDC_DN

GO Biological Process (0):

GO Molecular Function (2): PDZ domain binding (GO:0030165), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein domain specific binding	1
binding	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USHBP1	MCCC2	Q9HCC0	960
USHBP1	E9PNW1	E9PNW1	908
USHBP1	BTD	P43251	810
USHBP1	MCCC1	Q96RQ3	603
USHBP1	ZMAT4	Q9H898	535
USHBP1	GMCL1	Q96IK5	510
USHBP1	ZBTB25	P24278	487
USHBP1	BABAM1	Q9NWV8	446
USHBP1	MCC	P23508	414
USHBP1	ABHD8	Q96I13	397
USHBP1	RFTN1	Q14699	376
USHBP1	KPNA1	P52294	371
USHBP1	MAGEA11	P43364	338
USHBP1	FIBIN	Q8TAL6	335
USHBP1	MMRN2	Q9H8L6	335

IntAct

850 interactions, top by confidence:

A	B	Type	Score
DYDC1	USHBP1	psi-mi:“MI:0915”(physical association)	0.780
USHBP1	C1orf216	psi-mi:“MI:0915”(physical association)	0.780
COPS4	USHBP1	psi-mi:“MI:0915”(physical association)	0.780
C1orf216	USHBP1	psi-mi:“MI:0915”(physical association)	0.780
USHBP1	COPS4	psi-mi:“MI:0915”(physical association)	0.780
MAGEB4	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
MOS	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	TXLNA	psi-mi:“MI:0915”(physical association)	0.720
SYNJ2BP	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
BEX3	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	KLHL38	psi-mi:“MI:0915”(physical association)	0.720
TXLNB	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
CENPP	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
CCDC116	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	CCDC24	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	KRT38	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	MED4	psi-mi:“MI:0915”(physical association)	0.720
CCHCR1	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
MCRS1	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	ZFYVE26	psi-mi:“MI:0915”(physical association)	0.720
FAM110A	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	PARVG	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	IMP3	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	SEC14L4	psi-mi:“MI:0915”(physical association)	0.720
VPS28	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	MAGEB4	psi-mi:“MI:0915”(physical association)	0.720
TXLNA	USHBP1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (315): USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid), USHBP1 (Two-hybrid)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: Q3T1I3, Q8N6Y0, Q8R370

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	5	16.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	122
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4331 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17250275:T:TA	donor_gain	1.0000
19:17250276:C:A	donor_gain	1.0000
19:17250280:AGGGC:A	donor_gain	1.0000
19:17250313:T:TA	donor_gain	1.0000
19:17250410:GGGCG:G	acceptor_gain	1.0000
19:17250411:GGCG:G	acceptor_gain	1.0000
19:17250412:GCG:G	acceptor_gain	1.0000
19:17250412:GCGC:G	acceptor_loss	1.0000
19:17250413:CG:C	acceptor_gain	1.0000
19:17250413:CGC:C	acceptor_gain	1.0000
19:17250413:CGCTG:C	acceptor_loss	1.0000
19:17250414:GCTG:G	acceptor_loss	1.0000
19:17250415:C:CC	acceptor_gain	1.0000
19:17251576:TCCTA:T	donor_loss	1.0000
19:17251577:CCTAC:C	donor_loss	1.0000
19:17251578:CTAC:C	donor_loss	1.0000
19:17251578:CTACC:C	donor_loss	1.0000
19:17251579:TACC:T	donor_loss	1.0000
19:17251579:TACCT:T	donor_loss	1.0000
19:17251580:A:AC	donor_gain	1.0000
19:17251580:A:T	donor_loss	1.0000
19:17251580:ACCTG:A	donor_loss	1.0000
19:17251581:C:CC	donor_gain	1.0000
19:17251597:AAATC:A	donor_gain	1.0000
19:17251601:C:A	donor_gain	1.0000
19:17251700:GTGTC:G	acceptor_gain	1.0000
19:17251701:TGTC:T	acceptor_gain	1.0000
19:17251702:GTC:G	acceptor_gain	1.0000
19:17251702:GTCCT:G	acceptor_loss	1.0000
19:17251703:TC:T	acceptor_gain	1.0000

AlphaMissense

4516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17259369:C:A	K322N	0.958
19:17259369:C:G	K322N	0.958
19:17259415:A:G	L307P	0.954
19:17264270:G:C	S10R	0.947
19:17264270:G:T	S10R	0.947
19:17264272:T:G	S10R	0.947
19:17262837:A:C	F119L	0.944
19:17262837:A:T	F119L	0.944
19:17262839:A:G	F119L	0.944
19:17262646:A:G	L183P	0.943
19:17259394:A:G	L314P	0.935
19:17259382:A:G	L318P	0.933
19:17259348:G:C	S329R	0.932
19:17259348:G:T	S329R	0.932
19:17259350:T:G	S329R	0.932
19:17259402:A:C	N311K	0.931
19:17259402:A:T	N311K	0.931
19:17259326:C:G	A337P	0.922
19:17259304:A:G	L344P	0.909
19:17264124:A:C	S27R	0.907
19:17264124:A:T	S27R	0.907
19:17264126:T:G	S27R	0.907
19:17259397:A:G	L313P	0.904
19:17255542:A:G	L512P	0.899
19:17260012:A:G	L218P	0.896
19:17259320:C:G	A339P	0.892
19:17255485:A:G	L531P	0.889
19:17256496:A:G	I482T	0.889
19:17259302:C:G	A345P	0.880
19:17250409:A:G	L643P	0.879

dbSNP variants (sampled 300 via entrez): RS1000166186 (19:17256001 TCAAA>T), RS1000304838 (19:17251188 T>A,C,G), RS1000467902 (19:17266444 G>A,C), RS1000553602 (19:17260805 G>C), RS1001177979 (19:17255293 A>C), RS1001190141 (19:17266249 G>A,T), RS1001244532 (19:17259974 G>A), RS1001445109 (19:17254823 G>A), RS1001499308 (19:17265995 C>A), RS1001609572 (19:17256786 A>G), RS1001827974 (19:17265900 C>A,T), RS1002344665 (19:17261141 C>A), RS1002429046 (19:17253087 G>C), RS1002657787 (19:17257845 C>T), RS1002719897 (19:17258963 C>T)

Disease associations

OMIM: gene MIM:611810 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007394_2	Mitochondrial DNA copy number	1.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement

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
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
aflatoxin B2	increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases methylation	1
Azacitidine	decreases expression	1
Carbamazepine	affects expression	1
Valproic Acid	increases methylation	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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