MALRD1

Summary

MALRD1 (MAM and LDL receptor class A domain containing 1, HGNC:24331) is a protein-coding gene on chromosome 10p12.31, encoding MAM and LDL-receptor class A domain-containing protein 1 (Q5VYJ5). Enhances production and/or transport of FGF19 and thus has a role in regulation of bile acid synthesis.

This gene encodes a conserved protein that features multiple MAM (meprin-A5-protein tyrosine phosphatase mu) and LDLR A2 (low density lipoprotein receptor A2) domains. Expression of this gene is enriched in the small intestine and is upregulated during differentiation of a human cell line that exhibits properties of intestinal epithelial cells. The encoded protein has been shown to modulate production of FGF19 in a human intestinal cell line and may regulate bile acid metabolism in the liver. A synergistic interaction between an allele of this gene and the APOE E4 allele is associated with an elevated risk of Alzheimer’s disease in human patients.

Source: NCBI Gene 340895 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001142308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24331
Approved symbol	MALRD1
Name	MAM and LDL receptor class A domain containing 1
Location	10p12.31
Locus type	gene with protein product
Status	Approved
Aliases	bA265G8.2, Diet1
Ensembl gene	ENSG00000204740
Ensembl biotype	protein_coding
OMIM	617715
Entrez	340895

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000377265, ENST00000377266, ENST00000418367, ENST00000454679, ENST00000480707, ENST00000492202

RefSeq mRNA: 1 — MANE Select: NM_001142308 NM_001142308

CCDS: CCDS73071

Canonical transcript exons

ENST00000454679 — 40 exons

Exon	Start	End
ENSE00001473325	19567502	19567703
ENSE00001473330	19209268	19209680
ENSE00001473331	19204898	19205265
ENSE00001473332	19204308	19204413
ENSE00001592266	19607777	19607902
ENSE00001594787	19347771	19348018
ENSE00001597231	19323949	19324105
ENSE00001603732	19352006	19352297
ENSE00001656753	19730706	19730781
ENSE00001686684	19327563	19327673
ENSE00001707771	19450307	19450490
ENSE00001734459	19331369	19331582
ENSE00001735068	19595194	19595457
ENSE00001749178	19280047	19280223
ENSE00001752102	19283019	19283181
ENSE00001767443	19615857	19615923
ENSE00001783154	19389452	19389609
ENSE00001783869	19387528	19387773
ENSE00001795269	19257684	19257771
ENSE00001804507	19692282	19692361
ENSE00003576213	19692458	19692554
ENSE00003610813	19491517	19491645
ENSE00003644633	19531194	19531351
ENSE00003693286	19498485	19498646
ENSE00003714992	19088024	19088185
ENSE00003715581	19165637	19165810
ENSE00003716792	19203728	19203880
ENSE00003720804	19123492	19123593
ENSE00003723191	19146198	19146344
ENSE00003729552	19103979	19104075
ENSE00003730839	19136574	19136781
ENSE00003732472	19175208	19175328
ENSE00003732680	19734157	19734478
ENSE00003732981	19087840	19087934
ENSE00003740648	19124524	19124670
ENSE00003741590	19133856	19133948
ENSE00003747289	19048801	19049137
ENSE00003749675	19155075	19155172
ENSE00003750371	19066719	19066859
ENSE00003751304	19128221	19128387

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 97.56.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2596 / max 168.2951, expressed in 434 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104158	0.5612	215
205779	0.3660	165
104149	0.2982	20
104150	0.0342	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.56	gold quality
jejunal mucosa	UBERON:0000399	95.66	gold quality
duodenum	UBERON:0002114	90.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.39	gold quality
small intestine	UBERON:0002108	82.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.31	gold quality
jejunum	UBERON:0002115	75.05	gold quality
calcaneal tendon	UBERON:0003701	69.75	gold quality
adrenal tissue	UBERON:0018303	69.73	gold quality
sural nerve	UBERON:0015488	67.24	gold quality
descending thoracic aorta	UBERON:0002345	65.83	gold quality
left testis	UBERON:0004533	65.74	gold quality
popliteal artery	UBERON:0002250	65.70	gold quality
tibial artery	UBERON:0007610	65.66	gold quality
ventricular zone	UBERON:0003053	65.55	gold quality
adenohypophysis	UBERON:0002196	64.82	gold quality
testis	UBERON:0000473	64.71	gold quality
aorta	UBERON:0000947	64.27	gold quality
right atrium auricular region	UBERON:0006631	64.17	gold quality
right testis	UBERON:0004534	64.03	gold quality
cardiac atrium	UBERON:0002081	63.26	gold quality
tibial nerve	UBERON:0001323	62.97	gold quality
ascending aorta	UBERON:0001496	62.83	gold quality
right adrenal gland	UBERON:0001233	62.69	gold quality
thoracic aorta	UBERON:0001515	62.55	gold quality
pituitary gland	UBERON:0000007	62.14	gold quality
left ovary	UBERON:0002119	60.95	gold quality
tibialis anterior	UBERON:0001385	60.61	silver quality
right adrenal gland cortex	UBERON:0035827	60.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.22
E-GEOD-99795	no	5.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting MALRD1, 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-4482-3P	99.98	72.50	3147
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-3674	97.01	68.86	1171

Literature-anchored findings (GeneRIF, showing 3)

• Expression of these C10orf112 mRNA species was limited to a subset of brain regions and heart tissue (PMID:19103277)
• Diet1 appears to be a control point for the production of fibroblast growth factor 15/19 in enterocytes, and thus a regulator of bile acid and lipid homeostasis. (PMID:26045262)
• Clinical variability and probable founder effect in oculocutaneous albinism type 7. (PMID:31694064)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Malrd1	ENSMUSG00000075520
rattus_norvegicus	Malrd1	ENSRNOG00000052916

Paralogs (4): MDGA1 (ENSG00000112139), MDGA2 (ENSG00000139915), MAMDC2 (ENSG00000165072), MAMDC4 (ENSG00000177943)

Protein

Protein identifiers

MAM and LDL-receptor class A domain-containing protein 1 — Q5VYJ5 (reviewed: Q5VYJ5)

All UniProt accessions (4): B7ZBP3, H0Y3D6, Q5VYJ5, U5GXS0

UniProt curated annotations — full annotation on UniProt →

Function. Enhances production and/or transport of FGF19 and thus has a role in regulation of bile acid synthesis.

Subunit / interactions. Interacts with FGF19.

Subcellular location. Cytoplasmic vesicle membrane.

Tissue specificity. Strongly expressed in the small intestine.

RefSeq proteins (1): NP_001135780* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR000998	MAM_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR051560	MAM_domain-containing	Family

Pfam: PF00008, PF00057, PF00629

UniProt features (77 total): disulfide bond 32, domain 20, sequence variant 16, glycosylation site 4, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYJ5-F1	71.95	0.07

Functional residue map

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

Disulfide bonds (32): 40–58, 52–67, 434–446, 441–459, 453–470, 823–837, 831–850, 844–859, 1050–1063, 1057–1076, 1070–1085, 1264–1276, 1271–1289, 1283–1300, 1483–1495, 1490–1508, 1502–1517, 1684–1697, 1692–1710, 1704–1719 …

Glycosylation sites (4): 813, 1049, 1199, 1414

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_STEROL_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_KETONE_METABOLIC_PROCESS, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (2): cholesterol homeostasis (GO:0042632), negative regulation of bile acid biosynthetic process (GO:0070858)

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

GO Cellular Component (5): Golgi apparatus (GO:0005794), cytoplasmic vesicle membrane (GO:0030659), cytoplasm (GO:0005737), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
sterol homeostasis	1
bile acid biosynthetic process	1
negative regulation of steroid biosynthetic process	1
negative regulation of small molecule metabolic process	1
regulation of bile acid biosynthetic process	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

620 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MALRD1	FANK1	Q8TC84	476
MALRD1	CLIP3	Q96DZ5	462
MALRD1	ZBTB7C	A1YPR0	461
MALRD1	CHST8	Q9H2A9	452
MALRD1	PHKB	Q93100	436
MALRD1	NPIPB8	E9PQR5	430
MALRD1	NME8	Q8N427	424
MALRD1	ZNF555	Q8NEP9	422
MALRD1	NR1H4	Q96RI1	417
MALRD1	ZNF554	Q86TJ5	413
MALRD1	CYP7A1	P22680	410
MALRD1	APLP1	P51693	404
MALRD1	ADCY7	P51828	404
MALRD1	CACNA1B	Q00975	386
MALRD1	SUCLG2	Q96I99	384

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1D5NSM8, A0A1L8HYT7, A2AJX4, B1AUH1, B3DK56, B3EX02, E2RK30, E9PZ36, F1RWC3, F8W3R9, O54767, O60494, O70244, P08922, P08F94, P20239, P47984, P56677, P79953, P86091, P97435, P98072, P98073, P98074, Q0IIH7, Q0V8T3, Q0V8T5, Q2QI47, Q3UZ09, Q5VYJ5, Q63132, Q66TN7, Q6DIV5, Q6YI48, Q769J6, Q78DX7, Q7M761, Q7RTY7, Q7RTY8, Q7RTZ1

Diamond homologs: A2AJX4, B3EWZ5, B3EWZ6, B3EX02, C0HL13, O75581, O88572, P35953, P60755, P60756, P85171, P97435, P98072, P98073, P98074, Q0PMG2, Q0WYX8, Q2PC93, Q5VYJ5, Q7Z553, Q8NFP4, Q8QFX6, Q9GMT4, A2ARV4, A2VEC9, A6QNY1, G3V928, O75197, P07357, P0DSP1, P34434, P98155, P98156, P98157, P98158, P98160, P98162, P98164, P98165, P98166

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

7479 predictions. Top by Δscore:

Variant	Effect	Δscore
10:19065959:C:G	donor_gain	1.0000
10:19103971:T:A	acceptor_gain	1.0000
10:19103975:GCA:G	acceptor_loss	1.0000
10:19103976:CA:C	acceptor_loss	1.0000
10:19103977:AG:A	acceptor_gain	1.0000
10:19103977:AGGTT:A	acceptor_gain	1.0000
10:19103978:G:A	acceptor_loss	1.0000
10:19103978:GG:G	acceptor_gain	1.0000
10:19103978:GGT:G	acceptor_gain	1.0000
10:19103978:GGTT:G	acceptor_gain	1.0000
10:19103978:GGTTG:G	acceptor_gain	1.0000
10:19104073:ATG:A	donor_gain	1.0000
10:19104074:TG:T	donor_gain	1.0000
10:19104075:GG:G	donor_gain	1.0000
10:19104076:G:A	donor_loss	1.0000
10:19104076:G:GG	donor_gain	1.0000
10:19104077:T:G	donor_loss	1.0000
10:19123589:GAGAT:G	donor_gain	1.0000
10:19123591:GAT:G	donor_gain	1.0000
10:19123592:AT:A	donor_gain	1.0000
10:19123592:ATGT:A	donor_loss	1.0000
10:19123593:TGTA:T	donor_loss	1.0000
10:19123594:G:GG	donor_gain	1.0000
10:19123594:GT:G	donor_loss	1.0000
10:19123595:T:A	donor_loss	1.0000
10:19124522:A:AG	acceptor_gain	1.0000
10:19124523:G:GG	acceptor_gain	1.0000
10:19124523:GT:G	acceptor_gain	1.0000
10:19124523:GTGT:G	acceptor_gain	1.0000
10:19124656:G:GT	donor_gain	1.0000

AlphaMissense

14425 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:19209477:A:C	S930R	0.994
10:19209479:C:A	S930R	0.994
10:19209479:C:G	S930R	0.994
10:19209339:T:A	W884R	0.993
10:19209339:T:C	W884R	0.993
10:19209341:G:C	W884C	0.992
10:19209341:G:T	W884C	0.992
10:19209636:T:A	W983R	0.991
10:19209636:T:C	W983R	0.991
10:19692310:T:A	C2056S	0.991
10:19692311:G:C	C2056S	0.991
10:19205009:G:C	W774C	0.990
10:19205009:G:T	W774C	0.990
10:19209638:G:C	W983C	0.990
10:19209638:G:T	W983C	0.990
10:19204367:A:C	S722R	0.988
10:19204369:C:A	S722R	0.988
10:19204369:C:G	S722R	0.988
10:19209311:G:C	W874C	0.988
10:19209311:G:T	W874C	0.988
10:19327629:T:A	W1215R	0.988
10:19327629:T:C	W1215R	0.988
10:19498588:G:C	W1754C	0.988
10:19498588:G:T	W1754C	0.988
10:19205007:T:A	W774R	0.987
10:19205007:T:C	W774R	0.987
10:19327631:G:C	W1215C	0.987
10:19327631:G:T	W1215C	0.987
10:19567573:G:C	W1850C	0.986
10:19567573:G:T	W1850C	0.986

dbSNP variants (sampled 300 via entrez): RS1000003433 (10:19286818 T>G), RS1000003927 (10:19597020 G>T), RS1000007395 (10:19253645 C>A,T), RS1000011719 (10:19250521 G>A), RS1000012095 (10:19320153 A>G), RS1000026972 (10:19178489 C>G), RS1000036448 (10:19434324 T>C,G), RS1000042302 (10:19519320 A>G), RS1000045936 (10:19531072 T>C), RS1000047921 (10:19149058 T>C,G), RS1000049095 (10:19633082 A>T), RS1000050597 (10:19584385 C>A,G,T), RS1000056072 (10:19596794 G>A), RS1000058358 (10:19178764 G>A,T), RS1000060123 (10:19642937 T>C,G)

Disease associations

OMIM: gene MIM:617715 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003542_9	Night sleep phenotypes	6.000000e-06
GCST006629_28	Pulse pressure	4.000000e-16
GCST008460_5	Gout vs. Hyperuricemia	4.000000e-06
GCST010396_42	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST90006992_1	Gut microbiota relative abundance (unclassified genus belonging to family Clostridiaceae)	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0009104	hyperuricemia
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases methylation	2
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
tobacco tar	decreases reaction, increases expression	1
benzo(e)pyrene	decreases methylation	1
diallyl disulfide	decreases reaction, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Methapyrilene	decreases methylation	1
Phthalic Acids	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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