MTFR1L

Summary

MTFR1L (mitochondrial fission regulator 1 like, HGNC:28836) is a protein-coding gene on chromosome 1p36.11, encoding Mitochondrial fission regulator 1-like (Q9H019). Mitochondrial protein required for adaptation of miochondrial dynamics to metabolic changes.

Predicted to be involved in aerobic respiration and mitochondrial fission. Located in mitochondrion.

Source: NCBI Gene 56181 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001099625

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28836
Approved symbol	MTFR1L
Name	mitochondrial fission regulator 1 like
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000117640
Ensembl biotype	protein_coding
OMIM	620765
Entrez	56181

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 48 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000374300, ENST00000374301, ENST00000374303, ENST00000374307, ENST00000424294, ENST00000464008, ENST00000466284, ENST00000469815, ENST00000472643, ENST00000474295, ENST00000478284, ENST00000488327, ENST00000494293, ENST00000497956, ENST00000524618, ENST00000525713, ENST00000526158, ENST00000526894, ENST00000528624, ENST00000529116, ENST00000530599, ENST00000531361, ENST00000533762, ENST00000859602, ENST00000859603, ENST00000859604, ENST00000859605, ENST00000859606, ENST00000859607, ENST00000859608, ENST00000859609, ENST00000859610, ENST00000859611, ENST00000859612, ENST00000859613, ENST00000859614, ENST00000859615, ENST00000859616, ENST00000859617, ENST00000859618, ENST00000859619, ENST00000931849, ENST00000956474, ENST00000956475, ENST00000956476, ENST00000956477, ENST00000956478, ENST00000956479, ENST00000956480, ENST00000956481, ENST00000956482, ENST00000956483, ENST00000956484, ENST00000956485, ENST00000956486, ENST00000956487

RefSeq mRNA: 4 — MANE Select: NM_001099625 NM_001099625, NM_001099626, NM_001099627, NM_019557

CCDS: CCDS41284, CCDS44089

Canonical transcript exons

ENST00000374303 — 7 exons

Exon	Start	End
ENSE00001463108	25819954	25820029
ENSE00003509127	25826615	25826826
ENSE00003525974	25823019	25823128
ENSE00003586663	25826302	25826411
ENSE00003618062	25829509	25829830
ENSE00003669332	25823644	25823748
ENSE00003890734	25831921	25832938

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5231 / max 215.6569, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1544	13.4800	1809
1546	1.5865	861
1545	0.3195	152
1547	0.1370	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	98.78	gold quality
right adrenal gland cortex	UBERON:0035827	98.78	gold quality
left adrenal gland	UBERON:0001234	98.43	gold quality
left adrenal gland cortex	UBERON:0035825	98.39	gold quality
apex of heart	UBERON:0002098	98.11	gold quality
heart left ventricle	UBERON:0002084	97.93	gold quality
cardiac ventricle	UBERON:0002082	97.80	gold quality
adrenal gland	UBERON:0002369	97.73	gold quality
right atrium auricular region	UBERON:0006631	97.68	gold quality
adrenal cortex	UBERON:0001235	97.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.56	gold quality
left testis	UBERON:0004533	97.37	gold quality
gastrocnemius	UBERON:0001388	97.35	gold quality
cardiac atrium	UBERON:0002081	97.33	gold quality
metanephros cortex	UBERON:0010533	97.32	gold quality
heart	UBERON:0000948	97.12	gold quality
muscle of leg	UBERON:0001383	97.11	gold quality
lower esophagus	UBERON:0013473	97.09	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.09	gold quality
adrenal tissue	UBERON:0018303	97.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.82	gold quality
right testis	UBERON:0004534	96.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.77	gold quality
left ovary	UBERON:0002119	96.64	gold quality
right ovary	UBERON:0002118	96.61	gold quality
right frontal lobe	UBERON:0002810	96.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.41	gold quality
left ventricle myocardium	UBERON:0006566	96.25	gold quality
smooth muscle tissue	UBERON:0001135	96.19	gold quality
heart right ventricle	UBERON:0002080	96.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting MTFR1L, 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-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-4305	97.94	68.63	533
HSA-MIR-204-3P	97.80	66.84	1656

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtfr1l	ENSDARG00000003940
mus_musculus	Mtfr1l	ENSMUSG00000046671
rattus_norvegicus	Mtfr1l	ENSRNOG00000016937

Paralogs (2): MTFR1 (ENSG00000066855), MTFR2 (ENSG00000146410)

Protein

Protein identifiers

Mitochondrial fission regulator 1-like — Q9H019 (reviewed: Q9H019)

All UniProt accessions (13): A0A0S2Z5H6, C9JF50, E9PIF9, E9PJP7, E9PLD2, E9PLU1, E9PNJ0, E9PPF9, E9PPQ0, E9PRK5, E9PRW1, E9PSD6, Q9H019

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial protein required for adaptation of miochondrial dynamics to metabolic changes. Regulates mitochondrial morphology at steady state and mediates AMPK-dependent stress-induced mitochondrial fragmentation via the control of OPA1 levels.

Subcellular location. Mitochondrion outer membrane.

Post-translational modifications. Phosphorylated by AMPK. Upon stress, phosphorylation at Ser-103 and Ser-238 by AMPK is sufficient to induce mitochondrial fragmentation.

Similarity. Belongs to the MTFR1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H019-1	1	yes
Q9H019-2	2
Q9H019-3	3

RefSeq proteins (4): NP_001093095, NP_001093096, NP_001093097, NP_062457 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007972	Mtfr1	Family

Pfam: PF05308

UniProt features (20 total): modified residue 9, mutagenesis site 4, sequence conflict 3, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H019-F1	64.23	0.11

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 (9): 30, 41, 103, 110, 224, 225, 238, 261, 273

Mutagenesis-validated functional residues (4):

Position	Phenotype
103	loss of phosphorylation by ampk. no effect on mitochondrial morphology; when associated with a-238.
103	leads to fragmentation of mitochondrial network; when associated with d-238.
238	loss of phosphorylation by ampk. no effect on mitochondrial morphology; when associated with a-103.
238	leads to fragmentation of mitochondrial network; when associated with d-103.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ORGANELLE_FISSION, GOBP_MITOCHONDRIAL_FISSION, GOCC_MITOCHONDRIAL_ENVELOPE, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NRF2_01, GOBP_CELLULAR_RESPIRATION, HOXA4_Q2, STAT1_02, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B

GO Biological Process (2): mitochondrial fission (GO:0000266), aerobic respiration (GO:0009060)

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

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion organization	1
organelle fission	1
cellular respiration	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTFR1L	TATDN2	Q93075	570
MTFR1L	SLC12A8	A0AV02	486
MTFR1L	VPS33A	Q96AX1	471
MTFR1L	CSTF1	Q05048	461
MTFR1L	ARMC10	Q8N2F6	444
MTFR1L	MAIP1	Q8WWC4	430
MTFR1L	LAMTOR3	Q9UHA4	410
MTFR1L	MAVS	Q7Z434	407
MTFR1L	USP30	Q70CQ3	393
MTFR1L	ARMC1	Q9NVT9	392
MTFR1L	MICOS13	Q5XKP0	391
MTFR1L	PPP1R11	O60927	381
MTFR1L	RTF2	Q9BY42	373
MTFR1L	PIR	O00625	363
MTFR1L	NUP153	P49790	342

IntAct

81 interactions, top by confidence:

A	B	Type	Score
ARMC1	MTFR1L	psi-mi:“MI:0915”(physical association)	0.780
MTFR1L	ARMC1	psi-mi:“MI:0915”(physical association)	0.780
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
MTFR1L	MAGEA12	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	MTFR1L	psi-mi:“MI:0915”(physical association)	0.720
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
CNOT2	MTFR1L	psi-mi:“MI:0915”(physical association)	0.560
MTFR1L	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
MTFR1L	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
EFHC1	MTFR1L	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	MTFR1L	psi-mi:“MI:0915”(physical association)	0.560
MTFR1L	CNOT2	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SKP2	DPYSL4	psi-mi:“MI:0914”(association)	0.530
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
LRIG1	LRIG2	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (112): MTFR1L (Two-hybrid), MTFR1L (Two-hybrid), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), MTFR1L (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8ER70, A1L253, A2AHC3, A5WUN7, B1AZP2, D4AEC2, O14490, P28290, P62024, P97836, P97839, Q148W8, Q14CH0, Q2KI52, Q2M3X8, Q3ZBW7, Q4KM62, Q4R2Y2, Q4R707, Q52KF3, Q5PQL8, Q5R3Z9, Q5RD34, Q5RJX2, Q5VUB5, Q5VZP5, Q5XII9, Q6GLU8, Q6NSV7, Q6P995, Q6PEI3, Q6RFY2, Q7T3E8, Q8BJ42, Q8BYK5, Q8C1B1, Q922B9, Q95X94, Q96BN6, Q96KR7

Diamond homologs: B0K035, F1RCE7, G3V9A7, Q08BD8, Q0VFP3, Q3ZBW7, Q4V7T5, Q58CR1, Q5R3Z9, Q5RFN3, Q5XII9, Q6GP48, Q6P444, Q7T3E8, Q8VED8, Q99MB2, Q9CWE0, Q9H019, Q15390, Q9PTD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1359 predictions. Top by Δscore:

Variant	Effect	Δscore
1:25826824:CAGG:C	donor_loss	1.0000
1:25826825:AGGTA:A	donor_loss	1.0000
1:25826826:GG:G	donor_loss	1.0000
1:25826828:T:G	donor_loss	1.0000
1:25829826:GATCT:G	donor_gain	1.0000
1:25819948:G:GT	donor_gain	0.9900
1:25826607:T:A	acceptor_gain	0.9900
1:25826614:GGA:G	acceptor_gain	0.9900
1:25826614:GGAGT:G	acceptor_gain	0.9900
1:25826823:GCAG:G	donor_gain	0.9900
1:25826827:G:GG	donor_gain	0.9900
1:25829545:G:GT	donor_gain	0.9900
1:25829579:T:TA	acceptor_gain	0.9900
1:25829827:ATCT:A	donor_gain	0.9900
1:25829828:TCT:T	donor_gain	0.9900
1:25829828:TCTG:T	donor_loss	0.9900
1:25829829:CT:C	donor_gain	0.9900
1:25829829:CTGTA:C	donor_loss	0.9900
1:25829830:TGTAA:T	donor_loss	0.9900
1:25829831:G:GG	donor_gain	0.9900
1:25829832:T:TG	donor_loss	0.9900
1:25829833:AAG:A	donor_loss	0.9900
1:25829835:G:C	donor_loss	0.9900
1:25826609:GTCCA:G	acceptor_loss	0.9800
1:25826611:CCA:C	acceptor_loss	0.9800
1:25826612:CA:C	acceptor_loss	0.9800
1:25826612:CAGG:C	acceptor_gain	0.9800
1:25826613:A:AG	acceptor_gain	0.9800
1:25826613:AGGA:A	acceptor_gain	0.9800
1:25826613:AGGAG:A	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000255847 (1:25827210 TCA>T), RS1000340608 (1:25826522 T>C,G), RS1000503252 (1:25832922 A>C), RS1000591522 (1:25825434 T>G), RS1000637628 (1:25832672 C>T), RS1000734381 (1:25827739 G>A), RS1000750477 (1:25819216 C>T), RS1000816529 (1:25820482 CG>C), RS1000942467 (1:25820850 A>C), RS1000952371 (1:25821143 G>A), RS1001242604 (1:25830995 T>C), RS1001353047 (1:25824816 T>C), RS1001635576 (1:25818855 A>G), RS1002363128 (1:25820056 A>T), RS1002596297 (1:25822010 G>C)

Disease associations

OMIM: gene MIM:620765 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002403_40	Red blood cell count	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression, increases expression	1
Thiram	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ19	HAP1 MTFR1L (-) 1	Cancer cell line	Male
CVCL_XQ71	HAP1 MTFR1L (-) 2	Cancer cell line	Male
CVCL_XQ72	HAP1 MTFR1L (-) 3	Cancer cell line	Male
CVCL_XQ73	HAP1 MTFR1L (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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