REPS1

Summary

REPS1 (RALBP1 associated Eps domain containing 1, HGNC:15578) is a protein-coding gene on chromosome 6q24.1, encoding RalBP1-associated Eps domain-containing protein 1 (Q96D71). May coordinate the cellular actions of activated EGF receptors and Ral-GTPases.

This gene encodes a signaling adaptor protein with two EH domains that interacts with proteins that participate in signaling, endocytosis and cytoskeletal changes. The encoded protein has been found in association with intersectin 1 and Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 when intersectin 1 was isolated from clathrin-coated pits. The encoded protein has also been shown to interact with amphiphysin, a cytoplasmic protein at the surface of synaptic vesicles. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 85021 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodegeneration with brain iron accumulation 7 (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 285 total — 1 pathogenic
• Phenotypes (HPO): 26
• MANE Select transcript: NM_001286611

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15578
Approved symbol	REPS1
Name	RALBP1 associated Eps domain containing 1
Location	6q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135597
Ensembl biotype	protein_coding
OMIM	614825
Entrez	85021

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 35 protein_coding, 5 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000258062, ENST00000367663, ENST00000409812, ENST00000414243, ENST00000415951, ENST00000431346, ENST00000445570, ENST00000450536, ENST00000478483, ENST00000483468, ENST00000484164, ENST00000492787, ENST00000526022, ENST00000526244, ENST00000529423, ENST00000529597, ENST00000530255, ENST00000530370, ENST00000530575, ENST00000531675, ENST00000886445, ENST00000886446, ENST00000886448, ENST00000886449, ENST00000886450, ENST00000886452, ENST00000886454, ENST00000886456, ENST00000886458, ENST00000886460, ENST00000886462, ENST00000886464, ENST00000886466, ENST00000886467, ENST00000886469, ENST00000913792, ENST00000913793, ENST00000913794, ENST00000913795, ENST00000913796, ENST00000913797, ENST00000913798, ENST00000968035, ENST00000968036, ENST00000968037, ENST00000968038

RefSeq mRNA: 4 — MANE Select: NM_001286611 NM_001128617, NM_001286611, NM_001286612, NM_031922

CCDS: CCDS47488, CCDS5193, CCDS69212, CCDS69213

Canonical transcript exons

ENST00000450536 — 20 exons

Exon	Start	End
ENSE00001640608	138943513	138943576
ENSE00001761102	138944498	138944622
ENSE00001795052	138943853	138944015
ENSE00002150134	138903493	138905132
ENSE00002155006	138987530	138988253
ENSE00002191665	138945219	138945372
ENSE00002196547	138945501	138945697
ENSE00002477507	138947790	138947913
ENSE00003488622	138915858	138915976
ENSE00003488869	138914697	138914761
ENSE00003506671	138911276	138911371
ENSE00003529220	138907495	138907600
ENSE00003568871	138908668	138908816
ENSE00003597984	138926401	138926481
ENSE00003611547	138941335	138941489
ENSE00003617218	138917555	138917627
ENSE00003658797	138912765	138912950
ENSE00003661160	138920215	138920316
ENSE00003661635	138921037	138921124
ENSE00003667098	138929977	138930098

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6607 / max 127.4520, expressed in 1781 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75940	6.1093	1704
75938	3.4484	1426
75939	1.8183	1047
75941	1.2848	890

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.16	gold quality
right uterine tube	UBERON:0001302	98.02	gold quality
parotid gland	UBERON:0001831	97.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.80	gold quality
adenohypophysis	UBERON:0002196	96.64	gold quality
pituitary gland	UBERON:0000007	96.53	gold quality
ganglionic eminence	UBERON:0004023	96.36	gold quality
embryo	UBERON:0000922	96.35	gold quality
lower esophagus mucosa	UBERON:0035834	96.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.20	gold quality
cerebellar hemisphere	UBERON:0002245	96.18	gold quality
cerebellar cortex	UBERON:0002129	96.11	gold quality
cortical plate	UBERON:0005343	96.01	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.53	gold quality
skin of abdomen	UBERON:0001416	95.50	gold quality
right frontal lobe	UBERON:0002810	95.44	gold quality
skin of leg	UBERON:0001511	95.41	gold quality
right testis	UBERON:0004534	95.34	gold quality
cerebellum	UBERON:0002037	95.32	gold quality
left testis	UBERON:0004533	95.26	gold quality
testis	UBERON:0000473	94.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.58	gold quality
minor salivary gland	UBERON:0001830	94.43	gold quality
saliva-secreting gland	UBERON:0001044	94.41	gold quality
anterior cingulate cortex	UBERON:0009835	94.33	gold quality
ileal mucosa	UBERON:0000331	94.29	gold quality
zone of skin	UBERON:0000014	94.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.27	gold quality
body of uterus	UBERON:0009853	94.25	gold quality
primary visual cortex	UBERON:0002436	93.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting REPS1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
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-8063	99.91	69.76	3146
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3681-3P	99.88	70.46	2254

Literature-anchored findings (GeneRIF, showing 4)

• Inhibition of RALBP1 by polyclonal antibodies causes increased drug-accumulation and increased cytotoxicity which demonstrate the potential utility of targeting RALBP1 in the treatment of leukemia. (PMID:17143522)
• RALBP1 and ABCG2 transport doxorubicin differently in lung and breast cancer cell lines (PMID:17273774)
• SGIP1 and the signaling adaptor Reps1 interact with ITSN1 in vivo. (PMID:20946875)
• Phosphorylation of REPS1 at Ser709 by RSK attenuates the recycling of transferrin receptor. (PMID:33407999)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	reps1	ENSDARG00000002877
mus_musculus	Reps1	ENSMUSG00000019854
rattus_norvegicus	Reps1	ENSRNOG00000059224
drosophila_melanogaster	Dap160	FBGN0023388
drosophila_melanogaster	Eps-15	FBGN0035060
caenorhabditis_elegans		WBGENE00001224
caenorhabditis_elegans		WBGENE00006405

Paralogs (10): EHD3 (ENSG00000013016), EHD2 (ENSG00000024422), EPS15 (ENSG00000085832), EHD4 (ENSG00000103966), EHD1 (ENSG00000110047), EPS15L1 (ENSG00000127527), REPS2 (ENSG00000169891), SRL (ENSG00000185739), ITSN2 (ENSG00000198399), ITSN1 (ENSG00000205726)

Protein

Protein identifiers

RalBP1-associated Eps domain-containing protein 1 — Q96D71 (reviewed: Q96D71)

Alternative names: RalBP1-interacting protein 1

All UniProt accessions (10): E9PMG1, Q96D71, F2Z3L2, H0YCF0, H0YCR2, H0YDT0, H0YE73, H0YE89, H7C1V2, H7C225

UniProt curated annotations — full annotation on UniProt →

Function. May coordinate the cellular actions of activated EGF receptors and Ral-GTPases.

Subunit / interactions. Homodimer (Potential). Interacts with RAB11FIP2. Interacts with RALBP1, CRK and GRB2. Binding to RALBP1 does not affect its Ral-binding activity. Forms a complex with the SH3 domains of CRK and GRB2 which may link it to an EGF-responsive tyrosine kinase. Interacts with AMPH, ITSN1 (via SH3 domains) and SGIP1; may be involved in clathrin-mediated endocytosis.

Subcellular location. Membrane. Clathrin-coated pit.

Tissue specificity. Widely expressed with highest levels in heart and testis.

Post-translational modifications. EGF stimulates phosphorylation on Tyr-residues.

Disease relevance. Neurodegeneration with brain iron accumulation 7 (NBIA7) [MIM:617916] A neurodegenerative disorder associated with iron accumulation, primarily in the basal ganglia. Clinical features include speech and motor delay, truncal hypotonia, progressive cerebellar ataxia, and loss of ambulation. NBIA7 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96D71-1	1	yes
Q96D71-2	2
Q96D71-3	3
Q96D71-4	4

RefSeq proteins (4): NP_001122089, NP_001273540, NP_001273541, NP_114128 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000261	EH_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site

Pfam: PF12763

UniProt features (51 total): modified residue 18, compositionally biased region 11, region of interest 5, binding site 4, domain 3, splice variant 3, sequence conflict 3, sequence variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96D71-F1	57.83	0.23

Functional residue map

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

Ligand- & substrate-binding residues (4): 331; 333; 335; 342

Post-translational modifications (18): 143, 145, 162, 166, 170, 173, 272, 273, 288, 307, 475, 482, 489, 540, 544, 562, 709, 740

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 0 (showing top):

GO Biological Process (2): endocytosis (GO:0006897), endosomal transport (GO:0016197)

GO Molecular Function (5): calcium ion binding (GO:0005509), SH3 domain binding (GO:0017124), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
vesicle-mediated transport	2
membrane	2
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
intracellular transport	1
metal ion binding	1
protein domain specific binding	1
protein binding	1
molecular adaptor activity	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell periphery	1
endomembrane system	1

Protein interactions and networks

STRING

1128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REPS1	RALBP1	Q15311	834
REPS1	ADPGK	Q9BRR6	763
REPS1	RAB11FIP2	Q7L804	752
REPS1	DPAGT1	Q9H3H5	692
REPS1	RALA	P11233	670
REPS1	AATF	Q9NY61	630
REPS1	RALB	P11234	611
REPS1	ITSN1	Q15811	572
REPS1	CPNE1	Q99829	569
REPS1	IRGQ	Q8WZA9	562
REPS1	GTPBP2	Q9BX10	541
REPS1	DCAF17	Q5H9S7	536
REPS1	CRK	P46108	524
REPS1	GRB2	P29354	516
REPS1	MYO5B	Q9ULV0	504

IntAct

96 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
LDHB	LDHA	psi-mi:“MI:0914”(association)	0.800
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
LDHA	LDHC	psi-mi:“MI:0914”(association)	0.770
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
ARHGEF7	NCK2	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
HIP1R	HIP1	psi-mi:“MI:0914”(association)	0.640
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
AP2S1	AP2A2	psi-mi:“MI:0914”(association)	0.640
TRAPPC2L	TRAPPC13	psi-mi:“MI:0914”(association)	0.560
AP2B1	AP2A2	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
MYO6	POTEI	psi-mi:“MI:0914”(association)	0.530
REPS1	AP2B1	psi-mi:“MI:0914”(association)	0.530
DAB2	FCHO2	psi-mi:“MI:0914”(association)	0.530
RALBP1	AP2B1	psi-mi:“MI:0914”(association)	0.530
REPS1	AAK1	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
NUMB	REPS1	psi-mi:“MI:0915”(physical association)	0.500
Numb	REPS1	psi-mi:“MI:0915”(physical association)	0.500
BCR/ABL fusion	PIK3R2	psi-mi:“MI:0914”(association)	0.460

BioGRID (153): REPS1 (Two-hybrid), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), Numb (Affinity Capture-Western), REPS1 (Affinity Capture-MS), REPS1 (Co-fractionation), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), AAK1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2, A0JMU8, A1L1K8, A5D7H5, B9DFV2, E1BUG7, F4JP52, G1SW77, G3X9Z4, O08719, O15234, O94913, Q0V898, Q1LVV0, Q2T9I5, Q32NW2, Q3MHF8, Q498K9, Q566L7, Q5CZI8, Q5JVS0, Q5R4R4, Q5T8P6, Q5TYQ8, Q659C4, Q68FI1, Q6AXS5, Q6NVR8, Q6NZN0, Q6PKG0, Q8AVJ2, Q8CGC4, Q8K2F8, Q8K3W3, Q8K3X0, Q8NC51, Q8ND56, Q91W18, Q91W39, Q96D71

Diamond homologs: A1CBF3, A1DDY6, A2RA84, A3LPY4, A4QST9, A5DBE7, A5DZL0, A6R7X5, A6S9V4, A6ZPP1, A6ZZY3, A7EDF3, B0YC95, O14066, O42287, O54916, P34216, P36115, P47030, Q15811, Q1DKE6, Q2H9M1, Q4WG58, Q4WVH0, Q54KI4, Q59SR6, Q5BH85, Q60902, Q6BRH9, Q6C449, Q6C908, Q6CSC2, Q6FJW0, Q754G7, Q75AA0, Q7SB65, Q96D71, Q9NZM3, Q9UBC2, Q9WVE9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
WNT5A-dependent internalization of FZD4	6	56.4×	6e-08
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	6	47.0×	1e-07
The role of Nef in HIV-1 replication and disease pathogenesis	6	47.0×	1e-07
VLDLR internalisation and degradation	5	44.1×	3e-06
LDL clearance	6	40.3×	3e-07
Plasma lipoprotein clearance	5	29.4×	2e-05
Host Interactions of HIV factors	6	24.9×	4e-06
Lysosome Vesicle Biogenesis	5	20.1×	9e-05

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	9	80.6×	2e-13
clathrin-dependent endocytosis	10	58.7×	2e-13
synaptic vesicle endocytosis	10	43.6×	5e-12
regulation of endocytosis	5	24.3×	2e-04
endocytosis	10	9.6×	1e-05
intracellular protein transport	11	7.2×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	149
Likely benign	95
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
503503	NM_001286611.2(REPS1):c.232G>C (p.Val78Leu)	Pathogenic

SpliceAI

3775 predictions. Top by Δscore:

Variant	Effect	Δscore
6:138905129:CATC:C	acceptor_gain	1.0000
6:138905130:ATCC:A	acceptor_loss	1.0000
6:138905131:TC:T	acceptor_gain	1.0000
6:138905132:CC:C	acceptor_gain	1.0000
6:138905133:C:A	acceptor_loss	1.0000
6:138905134:T:C	acceptor_loss	1.0000
6:138907489:TATTA:T	donor_loss	1.0000
6:138907490:ATTAC:A	donor_loss	1.0000
6:138907491:TTACC:T	donor_loss	1.0000
6:138907492:TACCT:T	donor_loss	1.0000
6:138907493:ACC:A	donor_loss	1.0000
6:138907494:C:CT	donor_loss	1.0000
6:138907596:CAGAT:C	acceptor_gain	1.0000
6:138907597:AGATC:A	acceptor_loss	1.0000
6:138907598:GATC:G	acceptor_loss	1.0000
6:138907600:TCTG:T	acceptor_loss	1.0000
6:138907601:C:CC	acceptor_gain	1.0000
6:138907602:T:A	acceptor_loss	1.0000
6:138908663:ATTAC:A	donor_loss	1.0000
6:138908664:TTAC:T	donor_loss	1.0000
6:138908665:TACC:T	donor_loss	1.0000
6:138908666:ACC:A	donor_loss	1.0000
6:138908667:C:G	donor_loss	1.0000
6:138908812:TTGCT:T	acceptor_gain	1.0000
6:138908813:TGCT:T	acceptor_gain	1.0000
6:138908815:CT:C	acceptor_gain	1.0000
6:138908815:CTCTT:C	acceptor_loss	1.0000
6:138908817:C:CC	acceptor_gain	1.0000
6:138908817:CTTTA:C	acceptor_loss	1.0000
6:138908818:T:C	acceptor_gain	1.0000

AlphaMissense

5171 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:138905086:A:G	L790P	1.000
6:138905095:A:G	L787P	1.000
6:138905107:A:G	L783P	1.000
6:138907511:A:G	L769S	1.000
6:138907562:A:T	I752N	1.000
6:138912846:G:C	F630L	1.000
6:138912846:G:T	F630L	1.000
6:138912848:A:G	F630L	1.000
6:138926428:A:C	F437L	1.000
6:138926428:A:T	F437L	1.000
6:138926429:A:C	F437C	1.000
6:138926430:A:G	F437L	1.000
6:138941370:A:G	L367S	1.000
6:138941382:A:T	L363H	1.000
6:138941391:G:C	P360R	1.000
6:138941391:G:T	P360Q	1.000
6:138941394:A:G	L359S	1.000
6:138941408:C:A	K354N	1.000
6:138941408:C:G	K354N	1.000
6:138941410:T:C	K354E	1.000
6:138941415:G:T	A352D	1.000
6:138941416:C:G	A352P	1.000
6:138941418:A:T	V351D	1.000
6:138941421:A:T	V350E	1.000
6:138941424:A:C	L349R	1.000
6:138941424:A:G	L349P	1.000
6:138941424:A:T	L349Q	1.000
6:138941426:A:C	H348Q	1.000
6:138941426:A:T	H348Q	1.000
6:138941428:G:C	H348D	1.000

dbSNP variants (sampled 300 via entrez): RS1000025580 (6:138976335 A>G,T), RS1000044652 (6:138964218 TCCTA>T), RS1000163705 (6:138913604 T>A), RS1000181927 (6:138952260 T>A,C), RS1000186162 (6:138953512 C>G), RS1000205498 (6:138969437 A>C,T), RS1000207202 (6:138956457 T>C), RS1000259740 (6:138969058 G>C), RS1000265190 (6:138950525 C>T), RS1000275800 (6:138907262 G>C), RS1000296801 (6:138987860 AG>A), RS1000344578 (6:138946099 T>C), RS1000434798 (6:138932981 A>C,G), RS1000446222 (6:138923163 A>T), RS1000479052 (6:138937320 G>T)

Disease associations

OMIM: gene MIM:614825 | disease phenotypes: MIM:617916, MIM:234200

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodegeneration with brain iron accumulation 7	Limited	Unknown

Mondo (2): neurodegeneration with brain iron accumulation 7 (MONDO:0054763), neurodegeneration with brain iron accumulation (MONDO:0018307)

Orphanet (1): Neurodegeneration with brain iron accumulation (Orphanet:385)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000763	Sensory neuropathy
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001348	Brisk reflexes
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002061	Lower limb spasticity
HP:0002079	Hypoplasia of the corpus callosum
HP:0002415	Leukodystrophy
HP:0002503	Spinocerebellar tract degeneration
HP:0002505	Loss of ambulation
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0008936	Axial hypotonia
HP:0012675	Iron accumulation in brain
HP:0033643	Increased circulating very long-chain fatty acid concentration

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002868_7	Response to serotonin reuptake inhibitors in major depressive disorder	3.000000e-06
GCST010118_142	Type 2 diabetes	2.000000e-08
GCST010241_335	Apolipoprotein A1 levels	3.000000e-08
GCST010242_249	HDL cholesterol levels	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538421	Neurodegeneration with brain iron accumulation (NBIA) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17068112	REPS1		0.00	0

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases methylation	3
methylmercuric chloride	decreases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	affects phosphorylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	increases expression	1
coumarin	decreases phosphorylation	1
hydroquinone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Irinotecan	decreases expression, affects cotreatment, affects response to substance	1
Resveratrol	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	affects cotreatment, affects response to substance	1
Ivermectin	decreases expression	1
Methotrexate	increases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Thimerosal	increases expression	1
Thiram	increases expression	1
Tretinoin	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2J1	HAP1 REPS1 (-) 2	Cancer cell line	Male
CVCL_XS22	HAP1 REPS1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02587858	Not specified	UNKNOWN	NBIAready: Online Collection of Natural History Patient-reported Outcome Measures
NCT05522374	Not specified	RECRUITING	TIRCON International NBIA Registry
NCT05615571	Not specified	COMPLETED	Testing of NBIA Genes: Analysis of Genetic Heterogeneity and Validation of Mitochondrial Markers for Assessing Causality of Sequence Variants.
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.
NCT06596746	Not specified	RECRUITING	Neurodegenerative Diseases Progression Markers (MARKERS-NDD)