HERPUD2

Summary

HERPUD2 (HERPUD family member 2, HGNC:21915) is a protein-coding gene on chromosome 7p14.2, encoding Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (Q9BSE4). Could be involved in the unfolded protein response (UPR) pathway.

Predicted to be involved in endoplasmic reticulum unfolded protein response. Predicted to be located in membrane.

Source: NCBI Gene 64224 — RefSeq curated summary.

At a glance

• GWAS associations: 55
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_022373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21915
Approved symbol	HERPUD2
Name	HERPUD family member 2
Location	7p14.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22313
Ensembl gene	ENSG00000122557
Ensembl biotype	protein_coding
OMIM	620829
Entrez	64224

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000311350, ENST00000396081, ENST00000413517, ENST00000426180, ENST00000427455, ENST00000438224, ENST00000603731, ENST00000894703, ENST00000894704, ENST00000894705, ENST00000894706, ENST00000894707, ENST00000894708, ENST00000894709, ENST00000894710, ENST00000894711, ENST00000894712, ENST00000894713, ENST00000894714, ENST00000894715, ENST00000894716, ENST00000894717, ENST00000924127

RefSeq mRNA: 1 — MANE Select: NM_022373 NM_022373

CCDS: CCDS5446

Canonical transcript exons

ENST00000311350 — 9 exons

Exon	Start	End
ENSE00000832342	35670215	35670328
ENSE00000976571	35673201	35673278
ENSE00001023010	35694184	35694627
ENSE00001189319	35694801	35695135
ENSE00001523804	35632659	35633851
ENSE00003484715	35667434	35667588
ENSE00003549132	35634312	35634429
ENSE00003609476	35635135	35635458
ENSE00003689698	35638350	35638472

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 96.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.1722 / max 519.5978, expressed in 1818 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83557	16.5051	1789
83554	5.5807	1564
83550	3.4061	1542
83556	3.2064	1255
83551	2.9703	1510
83555	1.7595	1003
83559	1.0954	751
83548	0.7006	317
83553	0.4311	148
83552	0.4235	179

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	96.77	gold quality
caput epididymis	UBERON:0004358	96.65	gold quality
buccal mucosa cell	CL:0002336	96.52	gold quality
corpus epididymis	UBERON:0004359	96.29	gold quality
oral cavity	UBERON:0000167	96.00	gold quality
germinal epithelium of ovary	UBERON:0001304	95.95	gold quality
amniotic fluid	UBERON:0000173	95.38	gold quality
adult organism	UBERON:0007023	95.11	gold quality
synovial joint	UBERON:0002217	94.99	gold quality
trabecular bone tissue	UBERON:0002483	94.93	gold quality
superficial temporal artery	UBERON:0001614	94.45	gold quality
epithelial cell of pancreas	CL:0000083	94.30	gold quality
layer of synovial tissue	UBERON:0007616	93.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.84	gold quality
thymus	UBERON:0002370	93.77	gold quality
upper arm skin	UBERON:0004263	93.74	gold quality
epithelium of nasopharynx	UBERON:0001951	93.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.44	gold quality
penis	UBERON:0000989	93.35	gold quality
jejunal mucosa	UBERON:0000399	93.27	gold quality
superior surface of tongue	UBERON:0007371	93.11	gold quality
bone element	UBERON:0001474	92.97	gold quality
lower lobe of lung	UBERON:0008949	92.88	gold quality
cerebellar vermis	UBERON:0004720	92.86	gold quality
urethra	UBERON:0000057	92.79	gold quality
blood	UBERON:0000178	92.64	gold quality
upper leg skin	UBERON:0004262	92.55	gold quality
bone marrow	UBERON:0002371	92.49	gold quality
oocyte	CL:0000023	92.42	gold quality
oviduct epithelium	UBERON:0004804	92.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting HERPUD2, 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-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	herpud2	ENSDARG00000021033
mus_musculus	Herpud2	ENSMUSG00000008429
rattus_norvegicus	Herpud2	ENSRNOG00000029995
drosophila_melanogaster	Herp	FBGN0031950
caenorhabditis_elegans	tag-353	WBGENE00009112

Paralogs (1): HERPUD1 (ENSG00000051108)

Protein

Protein identifiers

Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein — Q9BSE4 (reviewed: Q9BSE4)

All UniProt accessions (5): C9J4Q7, C9JDD7, C9JV48, Q9BSE4, S4R420

UniProt curated annotations — full annotation on UniProt →

Function. Could be involved in the unfolded protein response (UPR) pathway.

Subcellular location. Membrane.

RefSeq proteins (1): NP_071768* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039751	HERPUD1/2	Family

Pfam: PF00240

UniProt features (19 total): strand 6, compositionally biased region 3, helix 2, turn 2, sequence variant 2, chain 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KDB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSE4-F1	61.82	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): AAGCAAT_MIR137, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_MALE_GAMETE_GENERATION, LHX3_01, CHX10_01, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, AFP1_Q6, MYB_Q3, ELK1_01, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, TAATTA_CHX10_01, ATGTACA_MIR493

GO Biological Process (3): spermatogenesis (GO:0007283), endoplasmic reticulum unfolded protein response (GO:0030968), response to unfolded protein (GO:0006986)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
response to topologically incorrect protein	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HERPUD2	INTS15	Q96N11	499
HERPUD2	FAM8A1	Q9UBU6	494
HERPUD2	OGFOD1	Q8N543	470
HERPUD2	TMUB2	Q71RG4	455
HERPUD2	OR4F6	Q8NGB9	433
HERPUD2	TMUB1	Q9BVT8	406
HERPUD2	NUDCD3	Q8IVD9	381
HERPUD2	OR52E4	Q8NGH9	379
HERPUD2	NT5DC4	Q86YG4	377
HERPUD2	MRM2	Q9UI43	373
HERPUD2	FBXO42	Q6P3S6	371
HERPUD2	SGSM2	O43147	370
HERPUD2	METTL25B	Q96FB5	370
HERPUD2	RNF185	Q96GF1	362
HERPUD2	ZDHHC4	Q9NPG8	362

IntAct

62 interactions, top by confidence:

A	B	Type	Score
HERPUD2		psi-mi:“MI:0915”(physical association)	0.560
	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
SLC35A4	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
HERPUD2	SLC39A9	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
HERPUD2	TAS2R10	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
ALG10	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
TMEM144	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
HERPUD2	IER3IP1	psi-mi:“MI:0915”(physical association)	0.560
NAF1	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
UBE2B	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
CYB561A3	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
SPTSSA	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
HERPUD2	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	HERPUD2	psi-mi:“MI:0915”(physical association)	0.560
GATAD1	SIN3B	psi-mi:“MI:0914”(association)	0.350
RNASEH2B	SAP18	psi-mi:“MI:0914”(association)	0.350
NEDD1	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
POLR1C	BDP1	psi-mi:“MI:0914”(association)	0.350
TMBIM6	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
SLC35A4	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
SLC39A9	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
IER3IP1	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
NAF1	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
UBE2B	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000
CYB561A3	HERPUD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): HERPUD2 (Affinity Capture-MS), HERPUD2 (Affinity Capture-MS), HERPUD2 (Affinity Capture-MS), HERPUD2 (Two-hybrid), HERPUD2 (Two-hybrid), HERPUD2 (Two-hybrid), HERPUD2 (Two-hybrid), IER3IP1 (Two-hybrid), TMEM60 (Two-hybrid), ALG10 (Two-hybrid), SLC7A1 (Two-hybrid), TMBIM6 (Two-hybrid), NAF1 (Two-hybrid), CYB561A3 (Two-hybrid), TMEM144 (Two-hybrid)

ESM2 similar proteins: A0A1L8GLK3, A0A974CYQ5, D2HWM5, D5LXJ0, P49950, P54731, Q0P5H8, Q15011, Q1LZE1, Q28DF1, Q3ZBU9, Q5HZY0, Q5R4I3, Q5R5B0, Q5XHH7, Q66HH4, Q6GPB6, Q6NRL6, Q6NYI0, Q6PCD5, Q6PCP5, Q6R755, Q7T321, Q7ZXQ3, Q803I8, Q80UY2, Q84L31, Q86TM6, Q8BGE4, Q8CIK8, Q8R317, Q8R3V6, Q8VCH8, Q924K2, Q92537, Q92575, Q96D05, Q9BSE4, Q9D882, Q9DBY1

Diamond homologs: Q0P5H8, Q15011, Q28DF1, Q5R5B0, Q66HH4, Q6NYI0, Q7ZXQ3, Q9BSE4, Q9JJC9, Q9JJK5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1572 predictions. Top by Δscore:

Variant	Effect	Δscore
7:35633847:CGCTC:C	acceptor_gain	1.0000
7:35633852:C:CC	acceptor_gain	1.0000
7:35633853:T:C	acceptor_gain	1.0000
7:35634310:A:AC	donor_gain	1.0000
7:35634310:A:C	donor_loss	1.0000
7:35634311:C:CC	donor_gain	1.0000
7:35634425:GGTGT:G	acceptor_gain	1.0000
7:35634427:TGT:T	acceptor_gain	1.0000
7:35634427:TGTC:T	acceptor_loss	1.0000
7:35634428:GT:G	acceptor_gain	1.0000
7:35634430:C:CC	acceptor_gain	1.0000
7:35634430:C:T	acceptor_loss	1.0000
7:35634435:C:CT	acceptor_gain	1.0000
7:35634436:A:T	acceptor_gain	1.0000
7:35634437:G:C	acceptor_gain	1.0000
7:35634437:G:GC	acceptor_gain	1.0000
7:35634442:A:AC	acceptor_gain	1.0000
7:35634442:A:C	acceptor_gain	1.0000
7:35635199:CAATG:C	donor_gain	1.0000
7:35635219:G:C	donor_gain	1.0000
7:35635238:T:TA	donor_gain	1.0000
7:35638348:A:AC	donor_gain	1.0000
7:35638349:C:CC	donor_gain	1.0000
7:35638349:CTA:C	donor_gain	1.0000
7:35638349:CTACT:C	donor_gain	1.0000
7:35667432:A:AC	donor_gain	1.0000
7:35667432:AC:A	donor_gain	1.0000
7:35667432:ACC:A	donor_gain	1.0000
7:35667433:C:CC	donor_gain	1.0000
7:35667433:CC:C	donor_gain	1.0000

AlphaMissense

2676 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:35670303:A:G	L84P	1.000
7:35673259:A:G	L56S	1.000
7:35694217:T:A	K38N	1.000
7:35694217:T:G	K38N	1.000
7:35694221:A:G	L37P	1.000
7:35633724:A:G	L396P	0.999
7:35635203:G:C	S291R	0.999
7:35635203:G:T	S291R	0.999
7:35635205:T:G	S291R	0.999
7:35670305:A:C	H83Q	0.999
7:35670305:A:T	H83Q	0.999
7:35670307:G:C	H83D	0.999
7:35670309:A:T	V82D	0.999
7:35673238:A:G	L63P	0.999
7:35673238:A:T	L63H	0.999
7:35673247:C:A	G60V	0.999
7:35673247:C:T	G60D	0.999
7:35673254:A:C	Y58D	0.999
7:35673256:A:T	V57E	0.999
7:35673264:C:A	Q54H	0.999
7:35673264:C:G	Q54H	0.999
7:35694209:A:G	L41P	0.999
7:35694218:T:A	K38I	0.999
7:35694237:A:G	W32R	0.999
7:35694237:A:T	W32R	0.999
7:35694290:A:T	I14N	0.999
7:35694296:A:G	L12P	0.999
7:35633728:A:G	S395P	0.998
7:35635157:C:G	G307R	0.998
7:35635157:C:T	G307R	0.998

dbSNP variants (sampled 300 via entrez): RS1000167416 (7:35692627 C>G,T), RS1000279058 (7:35650410 G>A), RS1000286267 (7:35650185 A>G), RS1000341804 (7:35637933 T>A,C), RS1000343012 (7:35637699 T>G), RS1000344036 (7:35662607 G>C), RS1000445704 (7:35644702 G>A,T), RS1000499007 (7:35673163 G>C), RS1000500429 (7:35662580 A>T), RS1000625897 (7:35657013 G>A), RS1000720248 (7:35656538 G>A), RS1000797452 (7:35686160 G>A), RS1000857747 (7:35674780 T>C), RS1000864699 (7:35681403 G>A), RS1000894050 (7:35639508 A>T)

Disease associations

OMIM: gene MIM:620829 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST001762_756	Obesity-related traits	9.000000e-06
GCST002386_6	Cognitive function	6.000000e-06
GCST007045_29	PR interval	4.000000e-10
GCST007226_11	PR interval	1.000000e-08
GCST010321_118	PR interval	6.000000e-22
GCST010774_14	Essential hypertension (time to event)	2.000000e-08
GCST010796_1307	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST010796_1308	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1309	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_1310	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_1311	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-10
GCST010796_3073	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-20
GCST010796_3074	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3075	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_3076	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3077	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-11
GCST010796_3078	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-13
GCST010796_3079	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-14
GCST010796_3080	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-14
GCST010796_3081	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-14
GCST010796_3082	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-14
GCST010796_3083	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-13
GCST010796_3084	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_3085	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_3086	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-10
GCST010796_3087	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_3088	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_3089	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-13
GCST010796_3090	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-14
GCST010796_3091	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003925	cognition
EFO:0004462	PR interval
EFO:0004918	age at diagnosis
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Coumestrol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SR26	HAP1 HERPUD2 (-) 1	Cancer cell line	Male
CVCL_XP52	HAP1 HERPUD2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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