RESP18

Summary

RESP18 (regulated endocrine specific protein 18, HGNC:33762) is a protein-coding gene on chromosome 2q35, encoding Regulated endocrine-specific protein 18 (Q5W5W9).

Predicted to act upstream of or within in utero embryonic development. Predicted to be located in Golgi apparatus and cytoplasmic vesicle. Predicted to be active in endoplasmic reticulum.

Source: NCBI Gene 389075 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 36 total

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33762
Approved symbol	RESP18
Name	regulated endocrine specific protein 18
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182698
Ensembl biotype	protein_coding
OMIM	612721
Entrez	389075

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000333527, ENST00000392083, ENST00000470719, ENST00000850999, ENST00000851000

RefSeq mRNA: 1 — MANE Select: None NM_001007089

CCDS: CCDS33382

Canonical transcript exons

ENST00000333527 — 7 exons

Exon	Start	End
ENSE00002464620	219333161	219333177
ENSE00003593030	219329637	219329764
ENSE00003594808	219327407	219327563
ENSE00003626418	219328924	219329008
ENSE00003637090	219330771	219330875
ENSE00003643897	219329163	219329252
ENSE00004283222	219332524	219332738

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 90.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3174 / max 50.9788, expressed in 77 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34073	0.2301	64
34072	0.0873	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	90.61	gold quality
putamen	UBERON:0001874	88.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.89	gold quality
caudate nucleus	UBERON:0001873	86.88	gold quality
hypothalamus	UBERON:0001898	76.64	gold quality
substantia nigra	UBERON:0002038	73.87	gold quality
Ammon’s horn	UBERON:0001954	73.15	gold quality
temporal lobe	UBERON:0001871	69.76	gold quality
amygdala	UBERON:0001876	69.72	gold quality
prefrontal cortex	UBERON:0000451	67.64	gold quality
anterior cingulate cortex	UBERON:0009835	66.74	gold quality
brain	UBERON:0000955	66.34	gold quality
cerebral cortex	UBERON:0000956	64.98	gold quality
primary visual cortex	UBERON:0002436	64.51	gold quality
frontal cortex	UBERON:0001870	64.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.21	gold quality
superior frontal gyrus	UBERON:0002661	62.05	gold quality
right frontal lobe	UBERON:0002810	60.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	59.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	48.11	gold quality
cerebellum	UBERON:0002037	47.93	gold quality
cerebellar cortex	UBERON:0002129	47.75	gold quality
cerebellar hemisphere	UBERON:0002245	47.74	gold quality
cortical plate	UBERON:0005343	45.71	gold quality
apex of heart	UBERON:0002098	45.42	gold quality
left testis	UBERON:0004533	44.30	gold quality
testis	UBERON:0000473	44.19	gold quality
right testis	UBERON:0004534	43.22	gold quality
colonic epithelium	UBERON:0000397	42.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting RESP18, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-934	98.49	70.44	581
HSA-MIR-5007-5P	97.95	64.71	614

Literature-anchored findings (GeneRIF, showing 4)

• RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose. (PMID:17951542)
• Over-expression of RESP18 resulted in aggravated cell death induced by dopaminergic neurotoxins. (PMID:23319378)
• RESP18HD is required for efficient sorting of ICA512 to secretory granules: RESP18HD is a key determinant for ICA512 granule targeting. (PMID:26836020)
• Identification of RESP18 Gene Mutations Linked to Hereditary Non-Syndromic Cleft Lip and Palate in a Southern Chinese Family. (PMID:38970244)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Resp18	ENSMUSG00000033061
rattus_norvegicus	Resp18	ENSRNOG00000019704

Protein

Protein identifiers

Regulated endocrine-specific protein 18 — Q5W5W9 (reviewed: Q5W5W9)

All UniProt accessions (1): Q5W5W9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Pancreas. Found in alpha, beta and delta cells in the pancreatic islets.

Miscellaneous. May be due to intron retention. Gene prediction based on RNA-Seq data. The CDS is using a non-AUG start codon.

Similarity. Belongs to the RESP18 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5W5W9-2	2, B	yes
Q5W5W9-1	1, A
Q5W5W9-3	3, C
Q5W5W9-4	4

RefSeq proteins (1): NP_001007090 (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024833	RESP18	Family
IPR029403	RESP18_dom	Domain

Pfam: PF14948

UniProt features (8 total): splice variant 7, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W5W9-F1	45.66	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, YOSHIMURA_MAPK8_TARGETS_UP, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NFE2L2.V2, HMG20B_TARGET_GENES, MIER1_TARGET_GENES, GSE10240_CTRL_VS_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, ZNF7_TARGET_GENES, GSE10240_IL22_VS_IL22_AND_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, GSE10240_IL17_VS_IL17_AND_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, GSE13306_RA_VS_UNTREATED_TREG_DN, GSE17721_CTRL_VS_GARDIQUIMOD_2H_BMDC_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
endomembrane system	2
intracellular membrane-bounded organelle	2
intracellular vesicle	1

Protein interactions and networks

STRING

902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RESP18	INS	P01308	422
RESP18	FABP9	Q0Z7S8	413
RESP18	FLYWCH2	Q96CP2	349
RESP18	TOR2A	Q5JU69	329
RESP18	PCSK2	P16519	324
RESP18	CIROZ	Q8N9H9	324
RESP18	OR5A1	Q8NGJ0	320
RESP18	PRLH	P81277	319
RESP18	CHGB	P05060	309
RESP18	IQSEC3	Q9UPP2	306
RESP18	RFPL2	O75678	288
RESP18	ODF4	Q2M2E3	269
RESP18	SLC60A1	Q8N468	269
RESP18	SMTNL2	Q2TAL5	255
RESP18	NPVF	Q9HCQ7	253

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GTK4, A0JNL8, A2RUT3, A4D1N5, A4D250, B1ANY3, C0HMD7, F1MQW7, F2Z3F1, J3KSC0, O14603, O95411, P0C092, P0DMR3, P37200, P47939, P47940, P69615, Q0VFX4, Q14695, Q32KZ5, Q3C1V9, Q4G0G2, Q4R3X9, Q52M75, Q53S99, Q5SR53, Q5SWW7, Q5T6R2, Q5W5W9, Q66669, Q66HF0, Q6AWC8, Q6DGF6, Q6ZP68, Q6ZV80, Q6ZVU0, Q7L4S7, Q7Z4H9, Q8N2C9

Diamond homologs: A0JNL8, P47939, P47940, P56722, Q16849, Q5W5W9, Q60673, Q63259

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

838 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219328922:A:AC	donor_gain	1.0000
2:219328923:C:CC	donor_gain	1.0000
2:219328923:CG:C	donor_gain	1.0000
2:219329251:CT:C	acceptor_gain	1.0000
2:219329253:C:CC	acceptor_gain	1.0000
2:219329631:CCTCA:C	donor_loss	1.0000
2:219329632:CTCA:C	donor_loss	1.0000
2:219329633:TCA:T	donor_loss	1.0000
2:219329636:C:CT	donor_loss	1.0000
2:219329666:T:A	donor_gain	1.0000
2:219329667:C:A	donor_gain	1.0000
2:219329671:T:TA	donor_gain	1.0000
2:219329760:CAGAC:C	acceptor_gain	1.0000
2:219329761:AGAC:A	acceptor_gain	1.0000
2:219329762:GAC:G	acceptor_gain	1.0000
2:219329762:GACCT:G	acceptor_loss	1.0000
2:219329763:ACC:A	acceptor_loss	1.0000
2:219329765:C:CC	acceptor_gain	1.0000
2:219329766:T:A	acceptor_loss	1.0000
2:219327562:CC:C	acceptor_gain	0.9900
2:219327562:CCCTA:C	acceptor_loss	0.9900
2:219327563:CC:C	acceptor_gain	0.9900
2:219327563:CCTA:C	acceptor_loss	0.9900
2:219327564:C:CC	acceptor_gain	0.9900
2:219327564:CT:C	acceptor_loss	0.9900
2:219327565:T:A	acceptor_loss	0.9900
2:219328915:AATAC:A	donor_loss	0.9900
2:219328916:ATAC:A	donor_loss	0.9900
2:219328917:TACT:T	donor_loss	0.9900
2:219328918:AC:A	donor_loss	0.9900

AlphaMissense

1494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219330811:G:C	F99L	0.880
2:219330811:G:T	F99L	0.880
2:219330813:A:G	F99L	0.880
2:219329757:G:C	F115L	0.867
2:219329757:G:T	F115L	0.867
2:219329759:A:G	F115L	0.867
2:219332672:G:C	F28L	0.837
2:219332672:G:T	F28L	0.837
2:219332674:A:G	F28L	0.837
2:219329754:C:A	W116C	0.834
2:219329754:C:G	W116C	0.834
2:219330826:A:C	F94L	0.816
2:219330826:A:T	F94L	0.816
2:219330828:A:G	F94L	0.816
2:219332573:G:C	F61L	0.809
2:219332573:G:T	F61L	0.809
2:219332575:A:G	F61L	0.809
2:219329217:A:C	F167L	0.799
2:219329217:A:T	F167L	0.799
2:219329219:A:G	F167L	0.799
2:219332735:G:C	F7L	0.776
2:219332735:G:T	F7L	0.776
2:219332737:A:G	F7L	0.776
2:219329756:A:G	W116R	0.770
2:219329756:A:T	W116R	0.770
2:219330841:C:A	W89C	0.727
2:219330841:C:G	W89C	0.727
2:219329655:G:C	F149L	0.709
2:219329655:G:T	F149L	0.709
2:219329657:A:G	F149L	0.709

dbSNP variants (sampled 300 via entrez): RS1000102781 (2:219327400 C>A,T), RS1000105538 (2:219336433 C>T), RS1000154315 (2:219336785 A>G), RS1000598062 (2:219332657 C>G,T), RS1000955954 (2:219328379 C>T), RS1001163344 (2:219327661 A>C), RS1001164120 (2:219338247 T>G), RS1001165898 (2:219333988 A>G), RS1001510748 (2:219337782 A>G), RS1001609816 (2:219333708 A>G), RS1001675240 (2:219330774 G>A), RS1001833481 (2:219336742 G>A), RS1002111924 (2:219335643 T>A), RS1002560414 (2:219334744 T>C), RS1002563151 (2:219329792 T>A,C)

Disease associations

OMIM: gene MIM:612721 | 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
GCST008839_309	Height	2.000000e-09
GCST011742_24	Triglyceride levels in HIV infection	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

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.