MRRF

Summary

MRRF (mitochondrial ribosome recycling factor, HGNC:7234) is a protein-coding gene on chromosome 9q33.2, encoding Ribosome-recycling factor, mitochondrial (Q96E11). Responsible for the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.

This gene encodes a ribosome recycling factor, which is a component of the mitochondrial translational machinery. The encoded protein, along with mitochondrial elongation factor 2, functions in ribosomal recycling at the termination of mitochondrial translation by mediating the disassembly of ribosomes from messenger RNA. A pseudogene of this gene has been identified on chromosome X.

Source: NCBI Gene 92399 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• GTEx eGene: eQTL in 9 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.11 (unconstrained)
• MANE Select transcript: NM_138777
• Interaction hub: 2,080 STRING partners (top 7% of genes corpus-wide)
• Notable: 52 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7234
Approved symbol	MRRF
Name	mitochondrial ribosome recycling factor
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	mtRRF, RRF
Ensembl gene	ENSG00000148187
Ensembl biotype	protein_coding
OMIM	604602
Entrez	92399

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 19 nonsense_mediated_decay, 18 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000344641

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 3, TSL 5: 3

ENST00000344641, ENST00000297908, ENST00000373723, ENST00000373724, ENST00000373727, ENST00000373728, ENST00000373729, ENST00000394315, ENST00000441707, ENST00000467864, ENST00000470366, ENST00000489572, ENST00000870638, ENST00000870639, ENST00000870640, ENST00000870641, ENST00000938375, ENST00000948156, ENST00000948157, ENST00000999010, ENST00000999011, ENST00000999012, ENST00000999013, ENST00000999014, ENST00000999015, ENST00000999016, ENST00000999017, ENST00000999018, ENST00001022446, ENST00001022447, ENST00001022448, ENST00001022449, ENST00001022450, ENST00001022451, ENST00001087000, ENST00001087001, ENST00001087002, ENST00001087003, ENST00001105018, ENST00001139819

RefSeq mRNA: 8 — MANE Select: NM_138777 NM_001173512, NM_001346339, NM_001346341, NM_001346343, NM_001346345, NM_001346347, NM_138777, NM_199177

CCDS: CCDS48013, CCDS55336, CCDS6840, CCDS87684

Canonical transcript exons

ENST00000344641 — 7 exons

Exon	Start	End
ENSE00001461421	122264882	122264938
ENSE00003520955	122313227	122313386
ENSE00003628261	122291749	122291840
ENSE00003707804	122280443	122280598
ENSE00003708440	122270864	122271075
ENSE00003784808	122285169	122285287
ENSE00004795638	122322540	122331337

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 94.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2767 / max 177.2784, expressed in 1813 samples.

Highest expression (Bgee): rectum, pancreatic ductal cell, lower esophagus mucosa, testis, metanephros cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MRRF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cortex	eqtl	2.4e-03	+0.25	9:122237673:G:C
Adipose Subcutaneous	eqtl	3.3e-03	+0.21	9:122264840:A:C
Colon Sigmoid	eqtl	5.2e-03	-0.42	9:122662487:C:G
Thyroid	sqtl	8.0e-03	+0.96	9:122451466:T:C
Esophagus Mucosa	eqtl	1.2e-02	+0.17	9:122264840:A:C
Brain Putamen basal ganglia	eqtl	1.9e-02	-0.31	9:121771910:A:C
Cells Cultured fibroblasts	eqtl	1.9e-02	+0.13	9:122264840:A:C
Whole Blood	eqtl	2.5e-02	+0.22	9:121387967:A:G
Artery Tibial	eqtl	3.9e-02	-0.10	9:122254264:G:A
Nerve Tibial	sqtl	4.6e-02	+0.56	9:121670738:C:T
Skin Sun Exposed Lower leg	eqtl	4.7e-02	+0.37	9:121882352:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
98402	19.9836	1809
98403	1.9499	1037
98401	0.3432	166

Top tissues by expression

showing 100 of 242 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	94.82	gold quality
pancreatic ductal cell	CL:0002079	94.14	silver quality
lower esophagus mucosa	UBERON:0035834	93.65	gold quality
left testis	UBERON:0004533	93.63	gold quality
metanephros cortex	UBERON:0010533	93.40	gold quality
right testis	UBERON:0004534	93.37	gold quality
mucosa of transverse colon	UBERON:0004991	93.00	gold quality
right uterine tube	UBERON:0001302	92.92	gold quality
gastrocnemius	UBERON:0001388	92.78	gold quality
muscle of leg	UBERON:0001383	92.59	gold quality
transverse colon	UBERON:0001157	92.49	gold quality
right lobe of liver	UBERON:0001114	92.18	gold quality
left lobe of thyroid gland	UBERON:0001120	91.78	gold quality
right lobe of thyroid gland	UBERON:0001119	91.77	gold quality
apex of heart	UBERON:0002098	91.71	gold quality
body of pancreas	UBERON:0001150	91.70	gold quality
esophagus mucosa	UBERON:0002469	91.69	gold quality
skin of leg	UBERON:0001511	91.60	gold quality
mucosa of stomach	UBERON:0001199	91.49	gold quality
skin of abdomen	UBERON:0001416	91.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.41	gold quality
islet of Langerhans	UBERON:0000006	91.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.29	gold quality
esophagus	UBERON:0001043	91.05	gold quality
heart left ventricle	UBERON:0002084	90.97	gold quality
thyroid gland	UBERON:0002046	90.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.92	gold quality
testis	UBERON:0000473	90.88	gold quality
right adrenal gland	UBERON:0001233	90.85	gold quality
right atrium auricular region	UBERON:0006631	90.69	gold quality
omental fat pad	UBERON:0010414	90.63	gold quality
adrenal tissue	UBERON:0018303	90.60	gold quality
peritoneum	UBERON:0002358	90.58	gold quality
left adrenal gland cortex	UBERON:0035825	90.58	gold quality
pancreas	UBERON:0001264	90.57	gold quality
left adrenal gland	UBERON:0001234	90.54	gold quality
lower esophagus	UBERON:0013473	90.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.48	gold quality
minor salivary gland	UBERON:0001830	90.45	gold quality
right adrenal gland cortex	UBERON:0035827	90.39	gold quality
cardiac ventricle	UBERON:0002082	90.37	gold quality
calcaneal tendon	UBERON:0003701	90.36	gold quality
small intestine	UBERON:0002108	90.11	gold quality
body of stomach	UBERON:0001161	90.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.08	gold quality
colon	UBERON:0001155	89.94	gold quality
intestine	UBERON:0000160	89.79	gold quality
adrenal gland	UBERON:0002369	89.74	gold quality
cardiac atrium	UBERON:0002081	89.70	gold quality
body of uterus	UBERON:0009853	89.67	gold quality
large intestine	UBERON:0000059	89.65	gold quality
skeletal muscle organ	UBERON:0014892	89.60	gold quality
ectocervix	UBERON:0012249	89.58	gold quality
zone of skin	UBERON:0000014	89.45	gold quality
heart	UBERON:0000948	89.42	gold quality
endocervix	UBERON:0000458	89.41	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.40	gold quality
adrenal cortex	UBERON:0001235	89.37	gold quality
vermiform appendix	UBERON:0001154	89.34	gold quality
upper lobe of left lung	UBERON:0008952	89.29	gold quality
spleen	UBERON:0002106	89.16	gold quality
colonic epithelium	UBERON:0000397	89.11	gold quality
smooth muscle tissue	UBERON:0001135	89.06	gold quality
adenohypophysis	UBERON:0002196	88.82	gold quality
monocyte	CL:0000576	88.74	gold quality
left ovary	UBERON:0002119	88.71	gold quality
cortex of kidney	UBERON:0001225	88.70	gold quality
tibial nerve	UBERON:0001323	88.67	gold quality
vagina	UBERON:0000996	88.62	gold quality
mouth mucosa	UBERON:0003729	88.56	gold quality
leukocyte	CL:0000738	88.52	gold quality
stomach	UBERON:0000945	88.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.42	gold quality
adult mammalian kidney	UBERON:0000082	88.32	gold quality
granulocyte	CL:0000094	88.24	gold quality
saliva-secreting gland	UBERON:0001044	88.12	gold quality
right ovary	UBERON:0002118	88.12	gold quality
sperm	CL:0000019	87.69	gold quality
pituitary gland	UBERON:0000007	87.60	gold quality
upper lobe of lung	UBERON:0008948	87.55	gold quality
left coronary artery	UBERON:0001626	87.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.52	gold quality
left uterine tube	UBERON:0001303	87.48	gold quality
tendon	UBERON:0000043	87.43	gold quality
gall bladder	UBERON:0002110	87.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.36	gold quality
cerebellar hemisphere	UBERON:0002245	87.35	gold quality
lymph node	UBERON:0000029	87.24	gold quality
cerebellar cortex	UBERON:0002129	87.19	gold quality
uterine cervix	UBERON:0000002	87.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.60	gold quality
coronary artery	UBERON:0001621	86.50	gold quality
tibial artery	UBERON:0007610	86.50	gold quality
popliteal artery	UBERON:0002250	86.49	gold quality
right lung	UBERON:0002167	86.48	gold quality
duodenum	UBERON:0002114	86.44	gold quality
aorta	UBERON:0000947	86.24	gold quality
ascending aorta	UBERON:0001496	86.17	gold quality
prostate gland	UBERON:0002367	86.17	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	30.1
Rectum	tissue	26.8	high
Skeletal muscle	tissue	26.4	high
Colon	tissue	23.5	high
Spinal cord	tissue	22.5
Duodenum	tissue	22.2	high
Parathyroid gland	tissue	21.8	high
Cerebral cortex	tissue	21.0	medium
Somatosensory cortex	tissue	21.0
Kidney	tissue	20.3	high
Occipital cortex	tissue	20.1
Pons	tissue	19.9
Medulla oblongata	tissue	19.6
Thalamus	tissue	19.2
Superior colliculi	tissue	19.2
Choroid plexus	tissue	19.1
Tonsil	tissue	19.1	medium
Midbrain	tissue	18.8
Breast	tissue	18.1	medium
Putamen	tissue	17.8
Prefrontal cortex	tissue	17.6
Substantia nigra	tissue	17.6
Hippocampal formation	tissue	17.5
Small intestine	tissue	17.4	high
Motor cortex	tissue	17.3
Septum	tissue	17.3
Retrosplenial and cingulate cortex	tissue	17.1
Temporal cortex	tissue	17.1
Heart muscle	tissue	17.0	high
Basal ganglia	tissue	16.9	medium
Entorhinal cortex	tissue	16.8
Esophagus	tissue	16.6	high
Ventral forebrain	tissue	16.6
Hypothalamus	tissue	16.4
Periaqueductal gray	tissue	16.2
Retrosplenial cortex	tissue	16.2
Urinary bladder	tissue	15.8	medium
Vagina	tissue	15.6	medium
Liver	tissue	15.5	high
Insular cortex	tissue	15.3
Corpus callosum	tissue	14.1
Skin 1	tissue	14.0	medium
Amygdala	tissue	13.9
Retina	tissue	13.4
Bone marrow	tissue	13.4	medium
Testis	tissue	13.2	high
Lymph node	tissue	13.1	medium
Frontal cortex	tissue	12.8
Thymus	tissue	12.8
Olfactory bulb	tissue	12.6
Epididymis	tissue	12.3	medium
Adrenal gland	tissue	12.3	high
Stomach 1	tissue	12.0	high
Thyroid gland	tissue	12.0	high
Pituitary gland	tissue	11.7
Caudate putamen	tissue	11.7
Appendix	tissue	11.4	high
Cerebellum	tissue	11.0	low
Adipose tissue	tissue	10.4	low
Postcentral gyrus	tissue	10.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (22.5), Dorsal spinal cord (20.7), Dorsal hippocampus (17.5), Ventral hippocampus (16.8), Subiculum (15.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MRRF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 51 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-6737-3P	98.95	68.56	1577

Functional genomics

gnomAD constraint: pLI 0.000144, LOEUF 1.11, missense Z 0.348 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000344641 — one region, missense o/e 1.01.

Literature-anchored findings (GeneRIF, showing 2)

• Depletion of mtRRF in human cell lines is lethal, initially causing profound mitochondrial dysmorphism, aggregation of mitoribosomes and elevated mitochondrial superoxide production. (PMID:18782833)
• EF-G2mt is an exclusive recycling factor in mammalian mitochondrial protein synthesis. (PMID:19716793)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrrf	ENSDARG00000034174
mus_musculus	Mrrf	ENSMUSG00000026887
rattus_norvegicus	Mrrf	ENSRNOG00000025997
drosophila_melanogaster	mRRF1	FBGN0035980
caenorhabditis_elegans	mrrf-1	WBGENE00020625

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0VCQ4	88.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
OR1J4	protein-coding	26219
OR1J2	protein-coding	26740
OR1J1	protein-coding	347168
PTGS1	protein-coding	5742
MORN5	protein-coding	254956
LHX6	protein-coding	26468
RBM18	protein-coding	92400
NDUFA8	protein-coding	4702

Protein

Protein identifiers

Ribosome-recycling factor, mitochondrial — Q96E11 (reviewed: Q96E11)

Alternative names: Ribosome-releasing factor, mitochondrial

All UniProt accessions (2): Q96E11, X6RDS5

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with GFM2. Promotes mitochondrial ribosome recycling by dissolution of intersubunit contacts.

Subcellular location. Mitochondrion.

Similarity. Belongs to the RRF family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q96E11-1	1	yes
Q96E11-2	2
Q96E11-3	3
Q96E11-4	4
Q96E11-5	5
Q96E11-6	6
Q96E11-7	7
Q96E11-8	8

RefSeq proteins (8): NP_001166983, NP_001333268, NP_001333270, NP_001333272, NP_001333274, NP_001333276, NP_620132, NP_954646 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002661	Ribosome_recyc_fac	Family
IPR023584	Ribosome_recyc_fac_dom	Domain
IPR036191	RRF_sf	Homologous_superfamily

Pfam: PF01765

UniProt features (27 total): splice variant 9, strand 7, helix 6, turn 2, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
7L20	Cryo-EM structure of the human 39S mitoribosomal subunit in complex with RRFmt and …	ELECTRON MICROSCOPY	3.15
7NSH	39S mammalian mitochondrial large ribosomal subunit with mtRRF (post) and mtEFG2	ELECTRON MICROSCOPY	3.2
7L08	Cryo-EM structure of the human 55S mitoribosome-RRFmt complex.	ELECTRON MICROSCOPY	3.49
6NU2	Structural insights into unique features of the human mitochondrial ribosome recycling	ELECTRON MICROSCOPY	3.9
6ZS9	Human mitochondrial ribosome in complex with ribosome recycling factor	ELECTRON MICROSCOPY	4
7NSI	55S mammalian mitochondrial ribosome with mtRRF (pre) and tRNA(P/E)	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E11-F1	78.38	0.45

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytokinetic bridge; microtubules

Antibody reliability (HPA): IH supported · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-5419276	Mitochondrial translation termination	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-5368287	Mitochondrial translation	—
R-HSA-72766	Translation	—

MSigDB gene sets: 121 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSLATION, CREB_Q4, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CREB_Q2_01, ATF4_Q2, MODULE_207, GOBP_ORGANELLE_DISASSEMBLY, CREBP1CJUN_01, CREB_01, GOCC_MITOCHONDRIAL_MATRIX, CGTSACG_PAX3_B, TGACGTCA_ATF3_Q6, CCGNMNNTNACG_UNKNOWN

GO Biological Process (2): translation (GO:0006412), ribosome disassembly (GO:0032790)

GO Molecular Function (2): ribosomal large subunit binding (GO:0043023), protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Mitochondrial translation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

14 GO namespaces:

Category	Terms
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
organelle disassembly	1
ribosome binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 6 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
ribosome disassembly	BP	direct assay
mitochondrion	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,080 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRRF	GFM2	Q969S9	987
MRRF	GFM1	Q96RP9	963
MRRF	TSFM	P43897	876
MRRF	ABCE1	P61221	814
MRRF	MIEF2	Q96C03	722
MRRF	TUFM	P49411	718
MRRF	EEF2	P13639	696
MRRF	MTRF1	O75570	662
MRRF	MTRF1L	Q9UGC7	661
MRRF	GTPBP2	Q9BX10	634
MRRF	ATP5IF1	Q9UII2	628
MRRF	HBS1L	Q9Y450	617
MRRF	MTIF2	P46199	599
MRRF	MTIF3	Q9H2K0	598
MRRF	GUF1	Q8N442	558

IntAct

Human interaction partners of MRRF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
DBT	association	0.620	3
AGTRAP	physical association	0.560	3
BANP	physical association	0.560	3
CMTM5	physical association	0.560	3
FAM9B	physical association	0.560	3
FHL3	physical association	0.560	3
KRT40	physical association	0.560	3
SYP	physical association	0.560	3
WIPI2	physical association	0.560	3
ZNF408	physical association	0.560	3
TRIM27	physical association	0.550	2
EFNB2	physical association	0.400	1
NAT1	association	0.350	1

BioGRID (344 interactions; top human partners by supporting records): DBT (Affinity Capture-MS; 4 records), CLPP (Proximity Label-MS; 3 records), HCCS (Affinity Capture-MS; 3 records), IBA57 (Affinity Capture-MS; 3 records), MMAB (Affinity Capture-MS; 3 records), MRRFP1 (Affinity Capture-MS; 3 records), NFS1 (Affinity Capture-MS; 3 records), TSFM (Proximity Label-MS; 3 records), ATPAF1 (Proximity Label-MS; 2 records), BANP (Two-hybrid; 2 records), CT55 (Affinity Capture-MS; 2 records), ICT1 (Proximity Label-MS; 2 records), LYRM7 (Affinity Capture-MS; 2 records), MRPL53 (Proximity Label-MS; 2 records), NDUFA2 (Proximity Label-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for MRRF: 52 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 793):

Position(s)	Effect	Δscore	Sites
9:122265542	donor_gain	1.0000
9:122280599–122280600	donor_loss	1.0000	5
9:122285168	acceptor_gain	1.0000
9:122285168	acceptor_loss	1.0000
9:122285288–122285289	donor_loss	1.0000	5
9:122313387–122313388	donor_loss	1.0000	5
9:122264939–122264940	donor_loss	0.9900	5
9:122265547	donor_gain	0.9900
9:122280442	acceptor_gain	0.9900	2
9:122285167	acceptor_loss	0.9900	2

AlphaMissense

383 missense substitutions predicted likely pathogenic (of 1,724 scored), across 130 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D229	8	0.868	0.958
F103	7	0.836	0.932
R190	6	0.933	0.992
K256	6	0.915	0.988
K205	6	0.911	0.986
M148	6	0.865	0.950
P171	6	0.849	0.975
M92	6	0.834	0.855
P183	6	0.822	0.885
M167	6	0.819	0.936
G175	6	0.802	0.931
V121	6	0.775	0.976
E188	6	0.725	0.850
E191	6	0.653	0.702
S134	5	0.925	0.986
K198	5	0.905	0.970
S165	5	0.878	0.971
V180	5	0.860	0.987
K195	5	0.825	0.897
R110	5	0.816	0.896

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.47e-09
Breast Invasive Carcinoma (TCGA)	unfavorable	0.0002

Disease associations

OMIM: gene MIM:604602 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tretinoin	decreases expression	2
Thapsigargin	decreases expression, increases reaction, increases expression	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
arsenite	increases reaction, affects binding	1
manganese chloride	increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
caffeic acid	decreases expression, increases reaction	1
4-methoxycinnamate methyl ester	increases reaction, decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Vorinostat	increases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Air Pollutants	increases expression, affects cotreatment, increases abundance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Atrazine	decreases expression	1
Drugs, Chinese Herbal	decreases expression, increases reaction	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
Ozone	increases expression, increases abundance, affects cotreatment	1
Phthalic Acids	decreases methylation	1
Tunicamycin	increases expression	1
Vanadates	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

5 trials:

NCT	Phase	Status	Title
NCT03600649	Phase 1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	Phase 1/2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	Phase 1/2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	Phase 1/2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis