HAPSTR2

Summary

HAPSTR2 (HUWE1 associated protein modifying stress responses 2, HGNC:55138) is a protein-coding gene on chromosome Xq27.1, encoding HUWE1-associated protein modifying stress responses 2 (A0A7P0TBJ1). Together with HAPSTR1 plays a central regulatory role in the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding.

Enables ubiquitin protein ligase binding activity. Involved in protein stabilization. Located in nucleus.

Source: NCBI Gene 389895 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001271560

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:55138
Approved symbol	HAPSTR2
Name	HUWE1 associated protein modifying stress responses 2
Location	Xq27.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000230707
Ensembl biotype	protein_coding
OMIM	301145
Entrez	389895

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000453380

RefSeq mRNA: 1 — MANE Select: NM_001271560 NM_001271560

CCDS: CCDS94678

Canonical transcript exons

ENST00000453380 — 1 exons

Exon	Start	End
ENSE00001799044	140091678	140092911

Expression profiles

Bgee: expression breadth ubiquitous, 109 present calls, max score 96.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.66	gold quality
right adrenal gland cortex	UBERON:0035827	78.21	gold quality
middle temporal gyrus	UBERON:0002771	77.46	gold quality
right adrenal gland	UBERON:0001233	77.26	gold quality
left adrenal gland	UBERON:0001234	76.87	gold quality
Brodmann (1909) area 23	UBERON:0013554	76.16	gold quality
left adrenal gland cortex	UBERON:0035825	75.60	gold quality
prefrontal cortex	UBERON:0000451	75.41	gold quality
anterior cingulate cortex	UBERON:0009835	74.73	gold quality
nucleus accumbens	UBERON:0001882	74.59	gold quality
caudate nucleus	UBERON:0001873	74.41	gold quality
putamen	UBERON:0001874	74.34	gold quality
adrenal cortex	UBERON:0001235	74.19	gold quality
secondary oocyte	CL:0000655	73.29	silver quality
right frontal lobe	UBERON:0002810	73.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.26	gold quality
ventricular zone	UBERON:0003053	73.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.00	gold quality
neocortex	UBERON:0001950	72.92	gold quality
frontal cortex	UBERON:0001870	72.62	gold quality
primary visual cortex	UBERON:0002436	72.30	gold quality
cerebral cortex	UBERON:0000956	71.67	gold quality
adrenal gland	UBERON:0002369	71.61	gold quality
amygdala	UBERON:0001876	70.47	gold quality
ganglionic eminence	UBERON:0004023	69.23	gold quality
temporal lobe	UBERON:0001871	69.13	gold quality
forebrain	UBERON:0001890	68.46	gold quality
entorhinal cortex	UBERON:0002728	68.31	gold quality
hypothalamus	UBERON:0001898	68.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting HAPSTR2, 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-3925-3P	100.00	69.95	1237
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-606	98.72	67.34	960
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-2682-3P	97.10	66.16	840

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hapstr1a	ENSDARG00000055383
mus_musculus	Gm715	ENSMUSG00000082226
rattus_norvegicus	Hapstr2	ENSRNOG00000043487
drosophila_melanogaster	CG4768	FBGN0030790
caenorhabditis_elegans	haps-1	WBGENE00016741

Paralogs (1): HAPSTR1 (ENSG00000182831)

Protein

Protein identifiers

HUWE1-associated protein modifying stress responses 2 — A0A7P0TBJ1 (reviewed: A0A7P0TBJ1)

All UniProt accessions (1): A0A7P0TBJ1

UniProt curated annotations — full annotation on UniProt →

Function. Together with HAPSTR1 plays a central regulatory role in the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding. Regulates these multiple stress response signaling pathways by stabilizing HAPSTR1, but also independently of HAPSTR1.

Subunit / interactions. Homooligomer. Heterooligomer with HAPSTR1; the interaction is direct and stabilizes HAPSTR1 independently of HUWE1. Interacts with HUWE1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in a tissue-restricted manner compared to HAPSTR1.

Similarity. Belongs to the HAPSTR1 family.

RefSeq proteins (1): NP_001258489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029196	HAPSTR1-like	Family
IPR040308	HAPR1	Family

Pfam: PF15251

UniProt features (10 total): region of interest 4, compositionally biased region 4, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A7P0TBJ1-F1	68.80	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
116	loss of homodimerization. loss of heterodimerization with hapstr1. no effect on interaction with huwe1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_BINDING, chrXq27, HSD17B8_TARGET_GENES, MIR1299, MIR7160_5P, MIR9500, MIR6128, MIR3663_3P, GSE11864_CSF1_PAM3CYS_VS_CSF1_IFNG_PAM3CYS_IN_MAC_DN, MIR6781_3P, MIR2682_3P

GO Biological Process (1): protein stabilization (GO:0050821)

GO Molecular Function (2): ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of protein stability	1
ubiquitin-like protein ligase binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A7P0TBJ1, A0A804C8T0, A2BE76, A2RRV3, A4IG66, A4IIE8, D4A4K3, O75182, P57095, P97578, Q02225, Q08AY9, Q09YG9, Q09YK4, Q1JPG0, Q28C41, Q2IBF8, Q2QL82, Q2QLF8, Q2QLG9, Q4QQM5, Q503U3, Q5BLE2, Q5M836, Q5XJS0, Q62141, Q62671, Q68EF0, Q6DFB7, Q6GR21, Q6NRB7, Q6P7D5, Q6PCG6, Q7L4E1, Q86YS3, Q8BG30, Q8BHS8, Q8BK03, Q8BQP8, Q8NAN2

Diamond homologs: A0A7P0TBJ1, A0A804C8T0, A2BE76, Q14AM7, Q14CZ0, Q28HY5, Q6PAX8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1796 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002778509 (X:140091958 G>A), RS1003145971 (X:140093186 T>G), RS1003196899 (X:140092615 G>A), RS1003241142 (X:140092401 G>C), RS1003955185 (X:140091733 G>C,T), RS1008096299 (X:140091093 G>A,T), RS1010140085 (X:140092892 A>G), RS1010213542 (X:140092433 G>A,C), RS1010546158 (X:140089688 C>T), RS1010665187 (X:140093256 T>G), RS1010797519 (X:140092634 G>A,T), RS1011618089 (X:140091558 G>A,T), RS1012177756 (X:140092598 T>G), RS1012306058 (X:140092053 C>T), RS1012902903 (X:140089677 G>A)

Disease associations

OMIM: gene MIM:301145 | 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)

Clinical trials (associated diseases)

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