RELCH

Summary

RELCH (RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing, HGNC:29289) is a protein-coding gene on chromosome 18q21.33, encoding RAB11-binding protein RELCH (Q9P260). Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP.

Involved in intracellular cholesterol transport. Located in recycling endosome and trans-Golgi network.

Source: NCBI Gene 57614 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 141 total — 1 pathogenic
• MANE Select transcript: NM_001346231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29289
Approved symbol	RELCH
Name	RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing
Location	18q21.33
Locus type	gene with protein product
Status	Approved
Aliases	HsT885, HsT3308, FLJ33841
Ensembl gene	ENSG00000134444
Ensembl biotype	protein_coding
OMIM	618001
Entrez	57614

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 14 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 2 non_stop_decay

ENST00000256858, ENST00000398130, ENST00000586920, ENST00000587198, ENST00000587714, ENST00000587725, ENST00000587764, ENST00000588446, ENST00000590713, ENST00000591227, ENST00000592479, ENST00000593217, ENST00000644646, ENST00000882911, ENST00000882912, ENST00000882913, ENST00000882914, ENST00000882915, ENST00000939326, ENST00000939327, ENST00000939328, ENST00000939329, ENST00000950689, ENST00000950690

RefSeq mRNA: 7 — MANE Select: NM_001346231 NM_001346229, NM_001346230, NM_001346231, NM_001346233, NM_001346234, NM_001346235, NM_020854

CCDS: CCDS11979, CCDS86675, CCDS86676

Canonical transcript exons

ENST00000644646 — 29 exons

Exon	Start	End
ENSE00000914760	62228305	62228598
ENSE00000950455	62257948	62258088
ENSE00000950456	62258512	62258676
ENSE00000950457	62261511	62261658
ENSE00000950458	62263989	62264145
ENSE00000950459	62264729	62264852
ENSE00000950460	62266701	62266749
ENSE00000950461	62268869	62268948
ENSE00000950463	62273980	62274086
ENSE00000950464	62275374	62275473
ENSE00000950470	62298790	62298860
ENSE00001011807	62255407	62255478
ENSE00001631273	62211153	62211242
ENSE00001737674	62227289	62227492
ENSE00001772216	62227598	62227689
ENSE00001785926	62221037	62221108
ENSE00003463222	62287351	62287467
ENSE00003510500	62221219	62221274
ENSE00003521005	62231194	62231269
ENSE00003538304	62282306	62282444
ENSE00003562618	62221384	62221497
ENSE00003591352	62232332	62232427
ENSE00003603359	62244764	62244876
ENSE00003630614	62280646	62280709
ENSE00003640410	62252664	62252754
ENSE00003664276	62279774	62279856
ENSE00003677090	62291543	62291631
ENSE00003825353	62187255	62188031
ENSE00003827934	62305414	62310249

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 95.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0476 / max 559.1893, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170510	31.6717	1812
170511	0.3760	149

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus mucosa	UBERON:0002469	95.51	gold quality
lower esophagus mucosa	UBERON:0035834	95.41	gold quality
rectum	UBERON:0001052	95.39	gold quality
upper arm skin	UBERON:0004263	95.37	gold quality
skin of abdomen	UBERON:0001416	94.22	gold quality
skin of leg	UBERON:0001511	93.93	gold quality
adrenal tissue	UBERON:0018303	93.76	gold quality
zone of skin	UBERON:0000014	93.24	gold quality
minor salivary gland	UBERON:0001830	93.24	gold quality
calcaneal tendon	UBERON:0003701	93.21	gold quality
vagina	UBERON:0000996	92.68	gold quality
mouth mucosa	UBERON:0003729	92.67	gold quality
oral cavity	UBERON:0000167	92.40	gold quality
epithelial cell of pancreas	CL:0000083	92.31	gold quality
right uterine tube	UBERON:0001302	92.26	gold quality
monocyte	CL:0000576	91.94	gold quality
bone marrow cell	CL:0002092	91.77	gold quality
nerve	UBERON:0001021	91.70	gold quality
tibial nerve	UBERON:0001323	91.70	gold quality
leukocyte	CL:0000738	91.46	gold quality
esophagus	UBERON:0001043	91.45	gold quality
vermiform appendix	UBERON:0001154	91.44	gold quality
adenohypophysis	UBERON:0002196	91.40	gold quality
body of pancreas	UBERON:0001150	91.34	gold quality
nasal cavity epithelium	UBERON:0005384	91.23	gold quality
corpus callosum	UBERON:0002336	91.18	gold quality
transverse colon	UBERON:0001157	91.17	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.15	gold quality
pituitary gland	UBERON:0000007	91.03	gold quality
saliva-secreting gland	UBERON:0001044	91.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.07
E-GEOD-99795	no	81.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

172 targeting RELCH, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 1)

• These data suggest that RELCH promotes nonvesicular cholesterol transport from recycling endosomes to the trans-Golgi network through membrane tethering. (PMID:29514919)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	relch	ENSDARG00000101443
mus_musculus	Relch	ENSMUSG00000026319
rattus_norvegicus	Relch	ENSRNOG00000015508

Protein

Protein identifiers

RAB11-binding protein RELCH — Q9P260 (reviewed: Q9P260)

Alternative names: LisH domain and HEAT repeat-containing protein KIAA1468, RAB11 binding and LisH domain, coiled-coil and HEAT repeat-containing, RAB11-binding protein containing LisH, coiled-coil, and HEAT repeats

All UniProt accessions (4): A0A075B768, A0A075B785, A0A2R8Y566, Q9P260

UniProt curated annotations — full annotation on UniProt →

Function. Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP. Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes.

Subcellular location. Recycling endosome. Golgi apparatus. trans-Golgi network.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P260-1	1	yes
Q9P260-2	2

RefSeq proteins (7): NP_001333158, NP_001333159, NP_001333160, NP_001333162, NP_001333163, NP_001333164, NP_065905 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006594	LisH	Conserved_site
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021133	HEAT_type_2	Repeat
IPR040362	RELCH	Family

UniProt features (32 total): modified residue 14, region of interest 4, compositionally biased region 3, repeat 3, coiled-coil region 2, splice variant 2, initiator methionine 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P260-F1	74.88	0.49

Functional residue map

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

Post-translational modifications (14): 2, 20, 22, 32, 54, 56, 180, 182, 183, 186, 385, 453, 792, 1149

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TATTATA_MIR374, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, PAX8_B, GOCC_TRANS_GOLGI_NETWORK, SOX9_B1, TGANTCA_AP1_C, IRF_Q6, NKX22_01, AACTTT_UNKNOWN, ELK1_01, GOBP_STEROL_TRANSPORT, GOBP_INTRACELLULAR_LIPID_TRANSPORT, DBP_Q6

GO Biological Process (2): intracellular cholesterol transport (GO:0032367), lipid transport (GO:0006869)

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

GO Cellular Component (5): trans-Golgi network (GO:0005802), recycling endosome (GO:0055037), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
intracellular anatomical structure	1
cholesterol transport	1
intracellular sterol transport	1
transport	1
lipid localization	1
binding	1
Golgi apparatus subcompartment	1
endosome	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1091 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RELCH	ZCCHC2	Q9C0B9	666
RELCH	RAB11A	P24410	534
RELCH	HAUS3	Q68CZ6	512
RELCH	RUFY2	Q8WXA3	506
RELCH	INTS4	Q96HW7	467
RELCH	RET	P07949	448
RELCH	PHLPP1	O60346	433
RELCH	KIAA1217	Q5T5P2	430
RELCH	STK36	Q9NRP7	429
RELCH	TNFRSF11A	Q9Y6Q6	426
RELCH	HEATR6	Q6AI08	423
RELCH	HEATR4	Q86WZ0	423
RELCH	TMEM253	P0C7T8	419
RELCH	SNX4	O95219	406
RELCH	DCC	P43146	405

IntAct

41 interactions, top by confidence:

A	B	Type	Score
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
MTM1	HLA-C	psi-mi:“MI:0914”(association)	0.350
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
CEACAM16	SBNO1	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
EPHA1	ENC1	psi-mi:“MI:0914”(association)	0.350
FPR1	NBAS	psi-mi:“MI:0914”(association)	0.350
HPN	DDX39A	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
RAB11A	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (82): KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), KIAA1468 (Proximity Label-MS), KIAA1468 (Proximity Label-MS)

ESM2 similar proteins: A0M8S0, A0M8T1, A0M8U1, A3KN28, A4D7R9, A9JRA0, P70398, Q00PJ0, Q07DV5, Q07DW9, Q07DX8, Q07DY8, Q07E08, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q09YN2, Q108U3, Q148V7, Q1RLU8, Q2IBA8, Q2IBD0, Q2IBE0, Q2IBE8, Q2PG42, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2QLG2, Q5R660, Q5R8N4, Q5XI83, Q68FW3, Q7Z3J2, Q86X10, Q8BWQ6

Diamond homologs: Q08BT5, Q148V7, Q6P6Y1, Q9P260

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	103
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
146258	GRCh38/hg38 18q21.33-23(chr18:61827111-80252149)x1	Pathogenic

SpliceAI

4831 predictions. Top by Δscore:

Variant	Effect	Δscore
18:62188027:GCTCA:G	donor_gain	1.0000
18:62188032:G:GG	donor_gain	1.0000
18:62220995:T:A	acceptor_gain	1.0000
18:62221214:A:AG	acceptor_gain	1.0000
18:62221371:A:AG	acceptor_gain	1.0000
18:62221375:T:TA	acceptor_gain	1.0000
18:62221378:TTCCA:T	acceptor_loss	1.0000
18:62221379:TCCA:T	acceptor_loss	1.0000
18:62221380:CCAG:C	acceptor_loss	1.0000
18:62221381:CAG:C	acceptor_loss	1.0000
18:62221382:A:AG	acceptor_gain	1.0000
18:62221383:G:GG	acceptor_gain	1.0000
18:62221383:GGA:G	acceptor_gain	1.0000
18:62221493:ATCAG:A	donor_loss	1.0000
18:62221494:TCAG:T	donor_loss	1.0000
18:62221495:CAGG:C	donor_loss	1.0000
18:62221496:AGGT:A	donor_loss	1.0000
18:62221497:GGTAA:G	donor_loss	1.0000
18:62221498:G:T	donor_loss	1.0000
18:62221499:T:G	donor_loss	1.0000
18:62227284:TTTA:T	acceptor_loss	1.0000
18:62227287:A:AG	acceptor_gain	1.0000
18:62227287:AG:A	acceptor_gain	1.0000
18:62227288:G:GT	acceptor_gain	1.0000
18:62227288:GG:G	acceptor_gain	1.0000
18:62227288:GGA:G	acceptor_gain	1.0000
18:62227288:GGAT:G	acceptor_gain	1.0000
18:62227288:GGATT:G	acceptor_gain	1.0000
18:62227490:GAG:G	donor_gain	1.0000
18:62227493:G:GG	donor_gain	1.0000

AlphaMissense

7924 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:62187798:C:A	A98D	1.000
18:62187807:T:C	L101P	1.000
18:62187834:C:A	A110D	1.000
18:62187837:T:C	L111P	1.000
18:62187843:T:C	L113P	1.000
18:62187855:T:C	L117P	1.000
18:62187885:T:A	L127Q	1.000
18:62187885:T:C	L127P	1.000
18:62187897:T:C	F131S	1.000
18:62221045:T:C	F209L	1.000
18:62221047:T:A	F209L	1.000
18:62221047:T:G	F209L	1.000
18:62221052:T:C	L211P	1.000
18:62221060:G:C	A214P	1.000
18:62221415:T:C	L259P	1.000
18:62221469:T:A	I277K	1.000
18:62227301:T:A	W291R	1.000
18:62227301:T:C	W291R	1.000
18:62227303:G:C	W291C	1.000
18:62227303:G:T	W291C	1.000
18:62227356:G:C	R309P	1.000
18:62232387:T:C	L527P	1.000
18:62232399:T:A	V531D	1.000
18:62232424:A:C	R539S	1.000
18:62232424:A:T	R539S	1.000
18:62244828:T:C	L562P	1.000
18:62244831:T:C	L563P	1.000
18:62244840:T:C	L566P	1.000
18:62244849:T:G	L569W	1.000
18:62244854:A:G	K571E	1.000

dbSNP variants (sampled 300 via entrez): RS1000015246 (18:62240225 T>C), RS1000037683 (18:62287675 G>A), RS1000082182 (18:62199767 C>T), RS1000084115 (18:62247340 A>G), RS1000095966 (18:62298007 T>A), RS1000153024 (18:62200164 A>G), RS1000191948 (18:62186282 C>T), RS1000217513 (18:62202026 G>A), RS1000252980 (18:62254307 G>A), RS1000307477 (18:62283625 A>G), RS1000319408 (18:62305326 G>A), RS1000332615 (18:62226090 T>C,G), RS1000390779 (18:62206734 C>T), RS1000411793 (18:62213468 C>T), RS1000441239 (18:62233539 G>C,T)

Disease associations

OMIM: gene MIM:618001 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007994_22	Asthma (age of onset)	2.000000e-10
GCST007995_6	Asthma (childhood onset)	9.000000e-09
GCST008152_128	Weight	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	2
Arsenic	decreases expression, increases abundance, affects methylation	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects binding, increases reaction	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Gallic Acid	decreases expression	1
Lead	increases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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