SAMM50

Summary

SAMM50 (SAMM50 sorting and assembly machinery component, HGNC:24276) is a protein-coding gene on chromosome 22q13.31, encoding Sorting and assembly machinery component 50 homolog (Q9Y512). Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes. It is a selective cancer dependency (DepMap: 58.3% of cell lines).

This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.

Source: NCBI Gene 25813 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 107 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 58.3% of screened cell lines
• MANE Select transcript: NM_015380

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24276
Approved symbol	SAMM50
Name	SAMM50 sorting and assembly machinery component
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	CGI-51, TRG-3, YNL026W, OMP85, TOB55, SAM50
Ensembl gene	ENSG00000100347
Ensembl biotype	protein_coding
OMIM	612058
Entrez	25813

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000350028, ENST00000465768, ENST00000474323, ENST00000493161, ENST00000493621, ENST00000494795, ENST00000854676, ENST00000854677, ENST00000937405, ENST00000937406, ENST00000937407, ENST00000943220, ENST00000943221, ENST00000943222, ENST00000943223

RefSeq mRNA: 1 — MANE Select: NM_015380 NM_015380

CCDS: CCDS14055

Canonical transcript exons

ENST00000350028 — 15 exons

Exon	Start	End
ENSE00000656936	43976055	43976183
ENSE00001390462	43955442	43955598
ENSE00001920991	43996338	43996529
ENSE00003476200	43981391	43981461
ENSE00003478097	43963286	43963396
ENSE00003493134	43989111	43989257
ENSE00003497020	43972236	43972342
ENSE00003508600	43968731	43968818
ENSE00003540282	43972871	43973001
ENSE00003553809	43964452	43964553
ENSE00003580187	43977872	43977958
ENSE00003582608	43976750	43976821
ENSE00003608710	43973236	43973323
ENSE00003639717	43990265	43990406
ENSE00003679796	43983933	43984000

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.3200 / max 230.9802, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192626	31.1588	1816
192624	5.0446	1701
192627	3.8697	1539
192625	0.2470	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.67	gold quality
vastus lateralis	UBERON:0001379	97.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.50	gold quality
quadriceps femoris	UBERON:0001377	97.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.32	gold quality
gastrocnemius	UBERON:0001388	97.31	gold quality
muscle of leg	UBERON:0001383	97.18	gold quality
muscle organ	UBERON:0001630	97.16	gold quality
diaphragm	UBERON:0001103	96.99	gold quality
skeletal muscle tissue	UBERON:0001134	96.76	gold quality
triceps brachii	UBERON:0001509	96.60	gold quality
body of tongue	UBERON:0011876	96.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.22	gold quality
muscle tissue	UBERON:0002385	96.09	gold quality
biceps brachii	UBERON:0001507	95.94	gold quality
deltoid	UBERON:0001476	95.91	gold quality
cervix squamous epithelium	UBERON:0006922	95.84	gold quality
gluteal muscle	UBERON:0002000	95.77	gold quality
apex of heart	UBERON:0002098	95.73	gold quality
right adrenal gland cortex	UBERON:0035827	95.67	gold quality
heart left ventricle	UBERON:0002084	95.58	gold quality
cardiac ventricle	UBERON:0002082	95.54	gold quality
right adrenal gland	UBERON:0001233	95.51	gold quality
left ventricle myocardium	UBERON:0006566	95.47	gold quality
left adrenal gland	UBERON:0001234	95.25	gold quality
right uterine tube	UBERON:0001302	95.12	gold quality
left adrenal gland cortex	UBERON:0035825	95.11	gold quality
nephron tubule	UBERON:0001231	95.08	gold quality
adrenal cortex	UBERON:0001235	94.96	gold quality
parotid gland	UBERON:0001831	94.91	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)

10 targeting SAMM50, 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-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-9899	91.24	59.59	90

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 58.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• The pathway of Voltage-dependent anion-selective channel biogenesis in human mitochondria involves the TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved. (PMID:17510655)
• mitofilin helps regulate mitochondrial morphology and at least four of the associated proteins (metaxins 1 and 2, SAM50 and CHCHD3) have been implicated in protein import (PMID:17624330)
• The study describes a novel role of SAM50 in maintaining the mitochondrial shape and the morphology of cristae. (PMID:22252321)
• Polymorphisms in the SAMM50 and PARVB genes in addition to those in the PNPLA3 gene were observed to be associated with the development and progression of NAFLD. (PMID:23535911)
• the integrity of MICOS and its efficient interaction with Sam50 are indispensable for cristae organization, which is relevant to mitochondrial function. (PMID:26530328)
• downregulation of SAM50 in BCR-ABL-expressing, but not normal CD34(+) human hematopoietic stem and progenitor cells (HSPCs) caused a significant decrease in growth, colony formation, and replating capacity. (PMID:26855047)
• SAMM50 affects the Drp1-dependent mitochondrial morphology. (PMID:27059175)
• Sub-mitochondrial localization of the genetic-tagged mitochondrial intermembrane space-bridging components Mic19, Mic60 and Sam50. (PMID:28808085)
• The authors results demonstrate that SNP in the SAMM50 gene is significantly associated with the presence and severity of NAFLD in a Korean populations. (PMID:29271184)
• Findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. (PMID:29307798)
• Sam50, the core component of the sorting and assembly machinery (SAM), is a critical regulator of mitochondrial dynamics and PINK1-Parkin-mediated mitophagy. (PMID:29874585)
• The role of SAMM50 in non-alcoholic fatty liver disease: from genetics to mechanisms. (PMID:33728819)
• SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components. (PMID:34037656)
• Effects of PNPLA3, TM6SF2 and SAMM50 on the development and severity of non-alcoholic fatty liver disease in children. (PMID:34490745)
• Loss of Sam50 in hepatocytes induces cardiolipin-dependent mitochondrial membrane remodeling to trigger mtDNA release and liver injury. (PMID:35313046)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	samm50l	ENSDARG00000039681
danio_rerio	samm50	ENSDARG00000045814
mus_musculus	Samm50	ENSMUSG00000022437
rattus_norvegicus	Samm50	ENSRNOG00000011952
drosophila_melanogaster	CG7639	FBGN0033989
caenorhabditis_elegans		WBGENE00001662

Protein

Protein identifiers

Sorting and assembly machinery component 50 homolog — Q9Y512 (reviewed: Q9Y512)

Alternative names: Transformation-related gene 3 protein

All UniProt accessions (1): Q9Y512

UniProt curated annotations — full annotation on UniProt →

Function. Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes. Required for the assembly of TOMM40 into the TOM complex.

Subunit / interactions. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with CHCHD3/MIC19. Interacts with ARMC1. (Microbial infection) Interacts with parasite T.gondii RH strain MAF1b1; the interaction is probably indirect and results in the disruption of the MIB complex and the formation of SPOTs (structures positive for outer mitochondrial membrane (OMM)), a cellular response to OMM stress, which leads to the constitutive shedding of OMM vesicles.

Subcellular location. Mitochondrion outer membrane. Cytoplasm. Mitochondrion.

Domain organisation. Its C-terminal part seems to contain many membrane-spanning sided beta-sheets, that have the potential to adopt a transmembrane beta-barrel type structure.

Similarity. Belongs to the SAM50/omp85 family.

RefSeq proteins (1): NP_056195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000184	Bac_surfAg_D15	Domain
IPR034746	POTRA	Domain
IPR039910	D15-like	Family

Pfam: PF01103

UniProt features (9 total): sequence conflict 3, sequence variant 2, chain 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6YOO	X-RAY DIFFRACTION	1.06
6YOP	X-RAY DIFFRACTION	1.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y512-F1	86.23	0.62

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 (1): 255

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-8949613	Cristae formation
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-162582	Signal Transduction
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9609507	Protein localization
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 172 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CRISTAE_FORMATION, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, GARY_CD5_TARGETS_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, MAF_Q6, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT

GO Biological Process (4): inner mitochondrial membrane organization (GO:0007007), protein import into mitochondrial matrix (GO:0030150), cristae formation (GO:0042407), protein insertion into mitochondrial outer membrane (GO:0045040)

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

GO Cellular Component (8): SAM complex (GO:0001401), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020), extracellular exosome (GO:0070062), MIB complex (GO:0140275), cytoplasm (GO:0005737), outer membrane (GO:0019867)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Protein localization	1
Mitochondrial biogenesis	1
RHO GTPase cycle	1
Organelle biogenesis and maintenance	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
mitochondrial membrane organization	1
protein transmembrane import into intracellular organelle	1
protein localization to mitochondrion	1
import into the mitochondrion	1
mitochondrial protein import pathway	1
inner mitochondrial membrane organization	1
outer mitochondrial membrane organization	1
protein insertion into mitochondrial membrane	1
binding	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
extracellular vesicle	1
inner mitochondrial membrane protein complex	1
intracellular anatomical structure	1
membrane	1

Protein interactions and networks

STRING

2538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMM50	TOMM40	O96008	986
SAMM50	CHCHD3	Q9NX63	986
SAMM50	MTX2	O75431	983
SAMM50	TOMM22	Q9NS69	968
SAMM50	IMMT	Q16891	967
SAMM50	MTX1	Q13505	918
SAMM50	PNPLA3	Q9NST1	911
SAMM50	TOMM20	Q15388	911
SAMM50	DNAJC11	Q9NVH1	871
SAMM50	MTX3	Q5HYI7	864
SAMM50	TOMM70	O94826	857
SAMM50	CHCHD6	Q9BRQ6	822
SAMM50	TIMM23	O14925	782
SAMM50	APOO	Q9BUR5	779
SAMM50	MICOS10	Q5TGZ0	766

IntAct

144 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
EXOC6	EXOC5	psi-mi:“MI:0914”(association)	0.840
SAMM50	CHCHD3	psi-mi:“MI:0915”(physical association)	0.780
CHCHD3	SAMM50	psi-mi:“MI:0915”(physical association)	0.780
IMMT	MTX2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
DNM1L	SAMM50	psi-mi:“MI:0915”(physical association)	0.600
SAMM50	DNM1L	psi-mi:“MI:0915”(physical association)	0.600
SAMM50	DNM1L	psi-mi:“MI:0407”(direct interaction)	0.600
CHCHD6	SAMM50	psi-mi:“MI:0915”(physical association)	0.560
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
CLEC5A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
TRAK1	MTX2	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
RAB8A	EXOC5	psi-mi:“MI:0914”(association)	0.510
ORF10	SAMM50	psi-mi:“MI:0915”(physical association)	0.480
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
SAMM50	MFN2	psi-mi:“MI:0915”(physical association)	0.400
Erh	BCLAF3	psi-mi:“MI:0915”(physical association)	0.400
MTX1	MTX2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (295): CHCHD3 (Two-hybrid), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Two-hybrid), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), RAB8A (Affinity Capture-MS)

ESM2 similar proteins: A2VE14, A5PLN9, A7MB28, B1WC68, O54865, O70133, O70496, P16068, P20595, P51798, P51799, Q02153, Q0VCB2, Q2HJ55, Q3TIR1, Q4PKH3, Q4R4U1, Q4R5H6, Q4ZHR9, Q5M887, Q5NVN7, Q5R5F8, Q5RCG0, Q5RES2, Q5RKN4, Q5U3I0, Q5VU57, Q5XIC4, Q6AXQ0, Q6AXV4, Q6AYR2, Q6P1X5, Q6P806, Q6PA35, Q7ZWS5, Q803G5, Q8BGH2, Q8BTG7, Q8MJJ1, Q8VH37

Diamond homologs: P46576, Q2HJ55, Q5U3I0, Q6AXV4, Q6P806, Q6PA35, Q7ZWS5, Q803G5, Q8BGH2, Q9Y512, P53969, Q10478, Q9V784

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SAMM50	“form complex”	“SAM complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
Cristae formation	8	27.1×	2e-07
Transport of vitamins, nucleosides, and related molecules	6	16.0×	3e-04
Mitochondrial biogenesis	9	14.8×	2e-06
Organelle biogenesis and maintenance	9	5.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cristae formation	7	52.3×	1e-08
inner mitochondrial membrane organization	8	47.8×	2e-09
mitochondrion organization	8	8.6×	9e-04
transmembrane transport	7	8.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

2360 predictions. Top by Δscore:

Variant	Effect	Δscore
22:43955595:CCGGG:C	donor_loss	1.0000
22:43955596:CGGGT:C	donor_loss	1.0000
22:43955597:GGGTA:G	donor_loss	1.0000
22:43963285:GA:G	acceptor_gain	1.0000
22:43963376:G:GT	donor_gain	1.0000
22:43963377:A:T	donor_gain	1.0000
22:43963392:AAGAT:A	donor_gain	1.0000
22:43963393:AGAT:A	donor_gain	1.0000
22:43963394:GAT:G	donor_gain	1.0000
22:43963394:GATG:G	donor_gain	1.0000
22:43963395:AT:A	donor_gain	1.0000
22:43963395:ATG:A	donor_loss	1.0000
22:43963396:TG:T	donor_loss	1.0000
22:43963397:G:GG	donor_gain	1.0000
22:43964447:TTTA:T	acceptor_loss	1.0000
22:43964448:TTA:T	acceptor_loss	1.0000
22:43964449:TAGGT:T	acceptor_loss	1.0000
22:43964450:A:AG	acceptor_gain	1.0000
22:43964450:A:T	acceptor_loss	1.0000
22:43964450:AG:A	acceptor_gain	1.0000
22:43964450:AGGT:A	acceptor_gain	1.0000
22:43964450:AGGTG:A	acceptor_gain	1.0000
22:43964451:G:GC	acceptor_loss	1.0000
22:43964451:G:GG	acceptor_gain	1.0000
22:43964451:GG:G	acceptor_gain	1.0000
22:43964451:GGT:G	acceptor_gain	1.0000
22:43964451:GGTG:G	acceptor_gain	1.0000
22:43964451:GGTGG:G	acceptor_gain	1.0000
22:43964553:GGTA:G	donor_loss	1.0000
22:43972231:TTTA:T	acceptor_loss	1.0000

AlphaMissense

3057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:43964459:T:A	V47D	1.000
22:43964468:T:A	V50D	0.999
22:43972266:T:A	V118D	0.999
22:43972272:T:C	F120S	0.999
22:43976104:G:C	R233P	0.999
22:43990327:G:T	G429W	0.999
22:43990355:C:A	A438D	0.999
22:43996375:T:C	F468L	0.999
22:43996377:C:A	F468L	0.999
22:43996377:C:G	F468L	0.999
22:43968783:T:C	F96S	0.998
22:43972894:T:A	N151K	0.998
22:43972894:T:G	N151K	0.998
22:43983965:G:A	G347E	0.998
22:43983967:T:C	F348L	0.998
22:43983969:C:A	F348L	0.998
22:43983969:C:G	F348L	0.998
22:43990321:G:T	G427W	0.998
22:43990322:G:A	G427E	0.998
22:43990328:G:A	G429E	0.998
22:43990371:T:A	N443K	0.998
22:43990371:T:G	N443K	0.998
22:43996366:G:T	G465W	0.998
22:43968743:T:C	S83P	0.997
22:43968752:G:C	A86P	0.997
22:43968756:G:C	R87P	0.997
22:43968765:T:C	L90S	0.997
22:43968782:T:C	F96L	0.997
22:43968784:T:A	F96L	0.997
22:43968784:T:G	F96L	0.997

dbSNP variants (sampled 300 via entrez): RS1000020388 (22:43991274 C>G), RS1000045511 (22:43977231 T>G), RS1000050112 (22:43991081 A>G), RS1000151542 (22:43959542 A>T), RS1000157701 (22:43976390 T>C), RS1000269235 (22:43982295 C>A,T), RS1000359202 (22:43963806 G>A), RS1000420820 (22:43969663 C>A,G), RS1000425612 (22:43987438 G>T), RS1000487724 (22:43996767 G>A), RS1000492778 (22:43977745 C>A,G,T), RS1000512317 (22:43986586 T>C), RS1000703203 (22:43974952 A>C), RS1000731994 (22:43989417 A>C), RS1000745442 (22:43981879 A>T)

Disease associations

OMIM: gene MIM:612058 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000248_9	Liver enzyme levels	8.000000e-16
GCST000583_15	Hematological and biochemical traits	2.000000e-12
GCST000583_18	Hematological and biochemical traits	2.000000e-12
GCST001275_2	Liver enzyme levels (alanine transaminase)	1.000000e-45
GCST001576_3	Nonalcoholic fatty liver disease	6.000000e-07
GCST001928_4	Pediatric non-alcoholic fatty liver disease activity score	2.000000e-20
GCST003302_6	Cholesterol, total	3.000000e-08
GCST004235_56	Total cholesterol levels	1.000000e-06
GCST005190_2	Nonalcoholic fatty liver disease	2.000000e-11
GCST005308_4	Nonalcoholic fatty liver disease	1.000000e-18
GCST005309_3	Nonalcoholic steatohepatitis-derived hepatocellular carcinoma	9.000000e-07
GCST006867_89	Type 2 diabetes	3.000000e-10
GCST007440_5	Alanine aminotransferase levels	7.000000e-06
GCST009391_324	Metabolite levels	7.000000e-06
GCST009391_330	Metabolite levels	9.000000e-06
GCST009391_339	Metabolite levels	3.000000e-06
GCST010396_46	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST90091033_8	Nonalcoholic fatty liver disease	7.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0004574	total cholesterol measurement
EFO:0010431	triacylglycerol 56:4 measurement
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0010433	triacylglycerol 56:6 measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066285 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.09	Kd	8.063	nM	CHEMBL5653589
8.09	ED50	8.063	nM	CHEMBL5653589
6.11	Kd	783.8	nM	CHEMBL3752910
6.11	ED50	783.8	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149339: Binding affinity to human SAMM50 incubated for 45 mins by Kinobead based pull down assay	kd	0.0081	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149339: Binding affinity to human SAMM50 incubated for 45 mins by Kinobead based pull down assay	kd	0.7838	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	affects expression, increases expression	2
Cyclosporine	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	decreases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652381	Binding	Binding affinity to human SAMM50 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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