MRFAP1

Summary

MRFAP1 (Morf4 family associated protein 1, HGNC:24549) is a protein-coding gene on chromosome 4p16.1, encoding MORF4 family-associated protein 1 (Q9Y605).

This gene encodes an intracellular protein that interacts with members of the MORF4/MRG (mortality factor on chromosome 4/MORF4 related gene) family and the tumor suppressor Rb (retinoblastoma protein.) The protein may play a role in senescence, cell growth and immortalization. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 93621 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_033296

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24549
Approved symbol	MRFAP1
Name	Morf4 family associated protein 1
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	PAM14, PGR1
Ensembl gene	ENSG00000179010
Ensembl biotype	protein_coding
OMIM	616905
Entrez	93621

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000320912, ENST00000382581, ENST00000507420, ENST00000512914, ENST00000885705, ENST00000947259

RefSeq mRNA: 2 — MANE Select: NM_033296 NM_001272053, NM_033296

CCDS: CCDS3389

Canonical transcript exons

ENST00000382581 — 2 exons

Exon	Start	End
ENSE00001384092	6640685	6641258
ENSE00001492672	6641730	6642729

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 138.6020 / max 1440.3867, expressed in 1826 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46780	135.4854	1826
46784	0.7258	391
46782	0.7072	375
46785	0.5732	232
46781	0.5630	279
46783	0.5475	289

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.97	gold quality
epithelial cell of pancreas	CL:0000083	99.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.91	gold quality
parietal pleura	UBERON:0002400	99.90	gold quality
middle temporal gyrus	UBERON:0002771	99.90	gold quality
visceral pleura	UBERON:0002401	99.89	gold quality
germinal epithelium of ovary	UBERON:0001304	99.88	gold quality
pons	UBERON:0000988	99.87	gold quality
postcentral gyrus	UBERON:0002581	99.87	gold quality
parietal lobe	UBERON:0001872	99.86	gold quality
superior vestibular nucleus	UBERON:0007227	99.86	gold quality
tibia	UBERON:0000979	99.84	gold quality
parotid gland	UBERON:0001831	99.84	gold quality
medulla oblongata	UBERON:0001896	99.84	gold quality
ventral tegmental area	UBERON:0002691	99.84	gold quality
palpebral conjunctiva	UBERON:0001812	99.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.83	gold quality
kidney epithelium	UBERON:0004819	99.83	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.82	gold quality
epithelium of nasopharynx	UBERON:0001951	99.82	gold quality
entorhinal cortex	UBERON:0002728	99.82	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.82	gold quality
subthalamic nucleus	UBERON:0001906	99.81	gold quality
substantia nigra pars compacta	UBERON:0001965	99.81	gold quality
inferior vagus X ganglion	UBERON:0005363	99.81	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.80	gold quality
lateral globus pallidus	UBERON:0002476	99.80	gold quality
esophagus squamous epithelium	UBERON:0006920	99.80	gold quality
globus pallidus	UBERON:0001875	99.79	gold quality
medial globus pallidus	UBERON:0002477	99.79	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	15.73
E-HCAD-13	no	3.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting MRFAP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-1305	99.91	71.43	3443
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-498-5P	99.76	69.64	1807

Literature-anchored findings (GeneRIF, showing 3)

• identify MRG15 residues that form a shallow hydrophobic pocket to interact with the N-terminal 50 residues of PAM14 through primarily hydrophobic interactions. (PMID:17008723)
• The results suggest that nucleus-localized Sedlin may play a role in regulation of transcriptional activities of the MRG family of transcription factors via binding to PAM14. (PMID:20108251)
• Blood DNA methylation and liver cancer in American Indians: evidence from the Strong Heart Study. (PMID:38010586)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mrfap1	ENSMUSG00000055302

Paralogs (2): MRFAP1L2 (ENSG00000170846), MRFAP1L1 (ENSG00000178988)

Protein

Protein identifiers

MORF4 family-associated protein 1 — Q9Y605 (reviewed: Q9Y605)

Alternative names: Protein PGR1, Protein associated with MRG of 14 kDa

All UniProt accessions (1): Q9Y605

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Found in a complex composed of MORF4L1, MRFAP1 and RB1. Interacts via its N-terminus with MORF4L1. Interacts with CSTB and MORF4L2.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

Similarity. Belongs to the MORF4 family-associated protein family.

RefSeq proteins (2): NP_001258982, NP_150638* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029254	MRFAP1	Family

Pfam: PF15155

UniProt features (2 total): chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y605-F1	82.44	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): TGACCTY_ERR1_Q2, ATGTTAA_MIR302C, TGTGTGA_MIR377, chr4p16, TSENG_IRS1_TARGETS_DN, AACTTT_UNKNOWN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FOXO4_02, GTGTGAG_MIR342, YATGNWAAT_OCT_C, TEF_Q6, FORTSCHEGGER_PHF8_TARGETS_DN, RAO_BOUND_BY_SALL4_ISOFORM_B, CREB3L4_TARGET_GENES, FOXG1_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (4): nucleoplasm (GO:0005654), perinuclear region of cytoplasm (GO:0048471), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

625 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRFAP1	MORF4L1	Q9UBU8	853
MRFAP1	MRGBP	Q9NV56	703
MRFAP1	ARL1	P40616	597
MRFAP1	MORF4L2	Q15014	586
MRFAP1	ARFGAP2	Q8N6H7	531
MRFAP1	KAT6B	Q8WYB5	523
MRFAP1	MMADHC	Q9H3L0	449
MRFAP1	MAF1	Q9H063	447
MRFAP1	TSEN54	Q7Z6J9	444
MRFAP1	TCHP	Q9BT92	411
MRFAP1	RPL13A	P40429	408
MRFAP1	TXNL1	O43396	400
MRFAP1	SLC25A3	Q00325	396
MRFAP1	NEDD8	Q15843	388
MRFAP1	TMEM270	Q6UE05	383

IntAct

276 interactions, top by confidence:

A	B	Type	Score
MRFAP1	MORF4L2	psi-mi:“MI:0915”(physical association)	0.950
MORF4L2	MRFAP1	psi-mi:“MI:0915”(physical association)	0.950
MORF4L1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.900
MRFAP1	MORF4L1	psi-mi:“MI:0915”(physical association)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MRFAP1	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.870
MRFAP1L1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.870
MRFAP1	MORF4L1	psi-mi:“MI:0915”(physical association)	0.850
MORF4L1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.850
BRK1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (139): MRFAP1 (Two-hybrid), MRFAP1 (Two-hybrid), MRFAP1 (Two-hybrid), MRFAP1 (Two-hybrid), MRFAP1L1 (Two-hybrid), GOLGA8G (Two-hybrid), C3orf62 (Two-hybrid), GOLGA8F (Two-hybrid), MRFAP1 (Two-hybrid), MRFAP1 (Affinity Capture-MS), MRFAP1 (Affinity Capture-MS), MORF4L2 (Two-hybrid), MRFAP1 (Affinity Capture-MS), MRFAP1 (Affinity Capture-MS), MRFAP1 (Affinity Capture-MS)

ESM2 similar proteins: A0RH02, A4IN75, A4J5G4, A5F4S8, A7Z571, A8FDR4, B0RP99, B7HAY0, B7I056, B7JI37, B9IUC0, C0H3Y7, C1EN48, C3L9C5, C3LSD6, C3P449, C5D2I1, P13966, P64455, P64456, P64457, P64458, P66732, P66733, P69957, P69958, P9WJ12, P9WJ13, Q16AJ3, Q18012, Q3BPS1, Q3ZC61, Q45060, Q4UY42, Q5KZP0, Q5QYI0, Q5WD36, Q637L7, Q65J23, Q6HFI9

Diamond homologs: B2RBV5, Q3ZC61, Q5M820, Q5RC01, Q96HT8, Q9CQL7, Q9Y605

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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.

GO biological processes:

GO term	Partners	Fold	FDR
neuron migration	5	11.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

311 predictions. Top by Δscore:

Variant	Effect	Δscore
4:6640705:GCGC:G	donor_gain	0.9900
4:6641255:GGCG:G	donor_gain	0.9900
4:6641256:GCG:G	donor_gain	0.9900
4:6641256:GCGG:G	donor_gain	0.9900
4:6641258:GGT:G	donor_loss	0.9900
4:6641259:G:GG	donor_gain	0.9900
4:6641259:GT:G	donor_loss	0.9900
4:6641260:T:G	donor_loss	0.9900
4:6641261:AA:A	donor_loss	0.9900
4:6640707:GC:G	donor_gain	0.9800
4:6641262:AGT:A	donor_loss	0.9800
4:6641724:CTTTA:C	acceptor_loss	0.9800
4:6641725:TTTA:T	acceptor_loss	0.9800
4:6641726:TTAG:T	acceptor_loss	0.9800
4:6641727:TA:T	acceptor_loss	0.9800
4:6640709:G:GG	donor_gain	0.9700
4:6640827:GAC:G	acceptor_gain	0.9700
4:6640826:A:AG	acceptor_gain	0.9600
4:6640827:G:GG	acceptor_gain	0.9600
4:6641728:A:AG	acceptor_gain	0.9400
4:6641729:G:GG	acceptor_gain	0.9400
4:6641797:A:T	donor_gain	0.9400
4:6640822:CAACA:C	acceptor_loss	0.9300
4:6640823:AACAG:A	acceptor_loss	0.9300
4:6640824:ACAG:A	acceptor_loss	0.9300
4:6640825:CAGAC:C	acceptor_loss	0.9300
4:6640826:AG:A	acceptor_loss	0.9300
4:6641263:G:C	donor_loss	0.9300
4:6640706:CGC:C	donor_gain	0.9200
4:6640707:GCG:G	donor_gain	0.9200

AlphaMissense

832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:6640942:T:C	F27S	0.998
4:6641044:A:T	D61V	0.998
4:6640933:T:C	F24S	0.996
4:6640941:T:C	F27L	0.996
4:6640943:T:A	F27L	0.996
4:6640943:T:G	F27L	0.996
4:6640929:G:C	D23H	0.995
4:6640957:T:A	I32N	0.995
4:6641043:G:C	D61H	0.995
4:6641044:A:C	D61A	0.995
4:6641053:T:A	L64H	0.995
4:6641053:T:C	L64P	0.995
4:6641212:T:C	L117P	0.995
4:6640945:T:A	L28Q	0.994
4:6641043:G:T	D61Y	0.994
4:6641079:G:C	A73P	0.994
4:6640930:A:T	D23V	0.993
4:6640933:T:G	F24C	0.993
4:6640945:T:C	L28P	0.993
4:6640975:A:T	D38V	0.993
4:6641193:G:C	A111P	0.993
4:6640932:T:C	F24L	0.992
4:6640934:C:A	F24L	0.992
4:6640934:C:G	F24L	0.992
4:6640942:T:G	F27C	0.992
4:6640957:T:G	I32S	0.992
4:6640930:A:C	D23A	0.991
4:6641065:A:T	K68I	0.990
4:6641082:T:C	S74P	0.990
4:6641203:T:C	L114P	0.990

dbSNP variants (sampled 300 via entrez): RS1000091111 (4:6642241 G>C), RS1000253392 (4:6642517 G>T), RS1000575974 (4:6639954 A>C,G), RS1001320778 (4:6642819 G>A), RS1001413469 (4:6643054 A>G), RS1001511220 (4:6640577 T>G), RS10023643 (4:6640676 C>A,G,T), RS1002861442 (4:6639750 A>T), RS1003407955 (4:6639892 G>A,C), RS1003439691 (4:6640383 T>C), RS1003521794 (4:6642855 C>G,T), RS1003602222 (4:6640534 G>A,C,T), RS1004419725 (4:6639659 C>G), RS1004751987 (4:6639468 C>A,G), RS1004838283 (4:6640829 C>A,T)

Disease associations

OMIM: gene MIM:616905 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	affects expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chloropicrin	affects expression	1
bromovanin	increases expression	1
bisphenol S	decreases expression, affects cotreatment	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Phthalic Acids	increases methylation	1
Thiram	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3B8	Abcam HEK293T MRFAP1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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