HUS1B

Summary

HUS1B (HUS1 checkpoint clamp component B, HGNC:16485) is a protein-coding gene on chromosome 6p25.3, encoding Checkpoint protein HUS1B (Q8NHY5).

The protein encoded by this gene is most closely related to HUS1, a component of a cell cycle checkpoint protein complex involved in cell cycle arrest in response to DNA damage. This protein can interact with the check point protein RAD1 but not with RAD9. Overexpression of this protein has been shown to induce cell death, which suggests a related but distinct role of this protein, as compared to the HUS1.

Source: NCBI Gene 135458 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 5 total — 2 pathogenic
• MANE Select transcript: NM_148959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16485
Approved symbol	HUS1B
Name	HUS1 checkpoint clamp component B
Location	6p25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188996
Ensembl biotype	protein_coding
OMIM	609713
Entrez	135458

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380907

RefSeq mRNA: 1 — MANE Select: NM_148959 NM_148959

CCDS: CCDS4470

Canonical transcript exons

ENST00000380907 — 1 exons

Exon	Start	End
ENSE00001486751	655939	657100

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 91.37.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.37	gold quality
buccal mucosa cell	CL:0002336	75.56	silver quality
sperm	CL:0000019	74.02	gold quality
tendon of biceps brachii	UBERON:0008188	72.95	silver quality
secondary oocyte	CL:0000655	72.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.83	gold quality
lower esophagus mucosa	UBERON:0035834	66.45	gold quality
granulocyte	CL:0000094	65.60	gold quality
gingival epithelium	UBERON:0001949	63.68	gold quality
trabecular bone tissue	UBERON:0002483	63.10	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.94	gold quality
bone marrow	UBERON:0002371	62.35	gold quality
gingiva	UBERON:0001828	61.84	gold quality
decidua	UBERON:0002450	61.75	silver quality
parotid gland	UBERON:0001831	61.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	61.43	silver quality
medial globus pallidus	UBERON:0002477	61.31	gold quality
oviduct epithelium	UBERON:0004804	61.11	silver quality
cartilage tissue	UBERON:0002418	61.08	silver quality
globus pallidus	UBERON:0001875	60.44	silver quality
nasal cavity epithelium	UBERON:0005384	60.20	gold quality
esophagus squamous epithelium	UBERON:0006920	59.73	gold quality
vena cava	UBERON:0004087	59.45	gold quality
pons	UBERON:0000988	59.07	gold quality
cerebellar vermis	UBERON:0004720	58.80	gold quality
lateral nuclear group of thalamus	UBERON:0002736	58.66	silver quality
biceps brachii	UBERON:0001507	57.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	57.47	gold quality
lateral globus pallidus	UBERON:0002476	57.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	57.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting HUS1B, 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-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302

Literature-anchored findings (GeneRIF, showing 3)

• HUS1B directly interacts with RAD1, but not RAD9 or HUS1, whereas HUS1 can bind RAD1, RAD9, and another molecule of HUS1, suggesting that HUS1B cannot simply substitute for HUS1 in the complex. (PMID:11944979)
• The HUS1B promoter is hypomethylated in the placentas of low-birth-weight infants. (PMID:26911255)
• Potentially functional variants in nucleotide excision repair pathway genes predict platinum treatment response of Chinese ovarian cancer patients. (PMID:32663249)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000101611
mus_musculus	Hus1b	ENSMUSG00000076430
drosophila_melanogaster	Hus1-like	FBGN0026417
caenorhabditis_elegans	hus-1	WBGENE00002042

Paralogs (1): HUS1 (ENSG00000136273)

Protein

Protein identifiers

Checkpoint protein HUS1B — Q8NHY5 (reviewed: Q8NHY5)

All UniProt accessions (1): Q8NHY5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with RAD1 and RAD9B.

Tissue specificity. Expressed strongly in testis, less in spleen, thymus, prostate, colon and leukocytes.

Similarity. Belongs to the HUS1 family.

RefSeq proteins (1): NP_683762* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007150	HUS1/Mec3	Family
IPR016580	HUS1	Family

Pfam: PF04005

UniProt features (4 total): sequence variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHY5-F1	89.70	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_TELOMERE_ORGANIZATION, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, chr6p25, GOBP_NUCLEOTIDE_EXCISION_REPAIR, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MITOTIC_DNA_INTEGRITY_CHECKPOINT_SIGNALING, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (7): telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), nucleotide-excision repair (GO:0006289), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), mitotic DNA replication checkpoint signaling (GO:0033314), meiotic DNA integrity checkpoint signaling (GO:0044778), DNA damage checkpoint signaling (GO:0000077)

GO Molecular Function (0):

GO Cellular Component (3): nucleolus (GO:0005730), checkpoint clamp complex (GO:0030896), site of double-strand break (GO:0035861)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA integrity checkpoint signaling	2
DNA metabolic process	1
telomere organization	1
recombinational repair	1
double-strand break repair	1
DNA repair	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
DNA replication checkpoint signaling	1
mitotic cell cycle	1
mitotic DNA integrity checkpoint signaling	1
mitotic G2/M transition checkpoint	1
meiotic cell cycle checkpoint signaling	1
meiotic cell cycle	1
signal transduction in response to DNA damage	1
nuclear lumen	1
intracellular membraneless organelle	1
condensed nuclear chromosome	1
nuclear protein-containing complex	1
site of DNA damage	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HUS1B	RAD9B	Q6WBX8	985
HUS1B	RAD9A	Q99638	931
HUS1B	RAD17	O75943	817
HUS1B	TOPBP1	Q92547	688
HUS1B	CENPBD1P	B2RD01	544
HUS1B	SMLR1	H3BR10	506
HUS1B	EXOC2	Q96KP1	491
HUS1B	MEIOB	Q8N635	467
HUS1B	CHEK1	O14757	438
HUS1B	DUSP22	Q9NRW4	435
HUS1B	HORMAD2	Q8N7B1	424
HUS1B	LIG4	P49917	412
HUS1B	MDC1	Q14676	410
HUS1B	GMDS	O60547	404
HUS1B	ATR	Q13535	402

IntAct

13 interactions, top by confidence:

A	B	Type	Score
HUS1B	ZBTB14	psi-mi:“MI:0914”(association)	0.530
HUS1B	RAD1	psi-mi:“MI:0914”(association)	0.530
HUS1B	MLF1	psi-mi:“MI:0915”(physical association)	0.400
MLF2	HUS1B	psi-mi:“MI:0915”(physical association)	0.400
HSF2	HUS1B	psi-mi:“MI:0915”(physical association)	0.400
HUS1B		psi-mi:“MI:0915”(physical association)	0.400
PSMD2	HUS1B	psi-mi:“MI:0915”(physical association)	0.400
HUS1B	FKBPL	psi-mi:“MI:0915”(physical association)	0.400
STUB1	HUS1B	psi-mi:“MI:0915”(physical association)	0.400
HUS1B	AARSD1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (28): RAD1 (Affinity Capture-MS), RAD9A (Affinity Capture-MS), ZBTB14 (Affinity Capture-MS), DNLZ (Affinity Capture-MS), PSME3 (Affinity Capture-MS), FAM192A (Affinity Capture-MS), PCDH7 (Affinity Capture-MS), HUS1B (Affinity Capture-Western), HUS1B (Affinity Capture-Western), RAD1 (Two-hybrid), HUS1B (Two-hybrid), HUS1B (Affinity Capture-Western), PSME3 (Affinity Capture-MS), RAD9A (Affinity Capture-MS), FAM192A (Affinity Capture-MS)

ESM2 similar proteins: A3R064, A7E3N7, E9Q6X9, G3V8H4, O70248, O88888, O95382, O96018, Q3V3V9, Q499V3, Q4KM32, Q4R5X9, Q58CQ5, Q58EX7, Q5TG30, Q60806, Q66H85, Q6F5E8, Q6IUP3, Q6P5E6, Q6P9Q4, Q6PGG2, Q6WBX7, Q76MJ5, Q80UU1, Q80XL1, Q8BIW9, Q8BWA8, Q8C6B2, Q8CJ00, Q8IW93, Q8K031, Q8NHY5, Q8TDZ2, Q8WVB6, Q91ZJ0, Q924T7, Q92502, Q969H4, Q96NY9

Diamond homologs: O60921, Q54NC0, Q8BQY8, Q8K572, Q8NHY5, Q9VN60, P78955

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2571270	GRCh37/hg19 6p25.3-25.2(chr6:393153-3751765)x1	Pathogenic
814767	GRCh37/hg19 6p25.3(chr6:156974-2208360)x1	Pathogenic

SpliceAI

216 predictions. Top by Δscore:

Variant	Effect	Δscore
6:656148:TGA:T	donor_gain	0.9600
6:656128:A:AC	donor_gain	0.9300
6:656129:C:CC	donor_gain	0.9300
6:656353:C:CT	donor_gain	0.8100
6:656354:C:CT	donor_gain	0.8000
6:656262:TGC:T	donor_gain	0.7800
6:656400:TCC:T	donor_gain	0.7700
6:656145:T:TA	donor_gain	0.7600
6:656358:T:TA	donor_gain	0.7500
6:656527:T:A	donor_gain	0.7300
6:656242:T:TA	donor_gain	0.7000
6:655999:C:CA	donor_gain	0.6900
6:656451:AGCGT:A	donor_gain	0.6700
6:656813:C:T	acceptor_gain	0.6300
6:656309:C:CC	acceptor_gain	0.6200
6:656436:T:A	donor_gain	0.6100
6:656416:TGCC:T	donor_gain	0.6000
6:656455:T:TA	donor_gain	0.6000
6:656274:T:A	donor_gain	0.5900
6:656452:G:C	donor_gain	0.5900
6:656400:T:TA	donor_gain	0.5800
6:656423:G:C	donor_gain	0.5800
6:656425:T:A	donor_gain	0.5700
6:656373:A:AC	donor_gain	0.5600
6:656142:T:TA	donor_gain	0.5500
6:656369:A:AC	donor_gain	0.5500
6:656370:C:CC	donor_gain	0.5500
6:656603:C:CT	donor_gain	0.5500
6:656602:C:CT	donor_gain	0.5400
6:656352:A:AC	donor_gain	0.5300

AlphaMissense

1797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:656936:A:C	F3L	0.982
6:656936:A:T	F3L	0.982
6:656938:A:G	F3L	0.982
6:656937:A:G	F3S	0.980
6:656339:A:C	S202R	0.971
6:656339:A:T	S202R	0.971
6:656341:T:G	S202R	0.971
6:656712:A:G	I78T	0.971
6:656333:A:C	F204L	0.967
6:656333:A:T	F204L	0.967
6:656335:A:G	F204L	0.967
6:656747:A:C	F66L	0.966
6:656747:A:T	F66L	0.966
6:656749:A:G	F66L	0.966
6:656756:G:C	F63L	0.961
6:656756:G:T	F63L	0.961
6:656758:A:G	F63L	0.961
6:656191:A:G	C252R	0.960
6:656931:G:T	A5D	0.956
6:656334:A:G	F204S	0.955
6:656748:A:G	F66S	0.954
6:656885:G:C	S20R	0.945
6:656885:G:T	S20R	0.945
6:656887:T:G	S20R	0.945
6:656712:A:C	I78S	0.943
6:656932:C:G	A5P	0.941
6:656610:A:T	L112H	0.940
6:656937:A:C	F3C	0.940
6:656877:A:T	V23D	0.938
6:656379:A:G	M189T	0.928

dbSNP variants (sampled 300 via entrez): RS1000339009 (6:659054 T>G), RS1001340694 (6:657771 A>G), RS1001873860 (6:658039 C>T), RS1003176227 (6:658166 C>G,T), RS1003336888 (6:655497 A>C,G,T), RS1006287886 (6:657080 C>T), RS1007510948 (6:657242 C>T), RS1007580342 (6:658674 T>A,C), RS1010186061 (6:657424 A>G), RS1010637598 (6:658572 A>G), RS1012153713 (6:655442 A>C), RS1013031986 (6:659069 G>T), RS1013507253 (6:656646 AG>A), RS1013831436 (6:656759 G>A), RS1013839348 (6:655620 T>C)

Disease associations

OMIM: gene MIM:609713 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001599_2	Aging	9.000000e-06
GCST009391_1548	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0010511	niacinamide measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases methylation, affects response to substance, increases expression	2
propionaldehyde	increases expression	1
2-butenal	increases expression	1
butyraldehyde	increases expression	1
licochalcone B	increases expression	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Methotrexate	decreases expression	1
Silicon Dioxide	increases expression	1
Urethane	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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