RAMAC

Summary

RAMAC (RNA guanine-7 methyltransferase activating subunit, HGNC:31022) is a protein-coding gene on chromosome 15q25.2, encoding RNA guanine-N7 methyltransferase activating subunit (Q9BTL3). Regulatory subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5’-cap structure of mRNAs.

Enables RNA binding activity and enzyme activator activity. Involved in 7-methylguanosine mRNA capping. Located in nucleus. Part of mRNA cap methyltransferase RNMT:RAMAC complex and mRNA capping enzyme complex.

Source: NCBI Gene 83640 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_031452

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31022
Approved symbol	RAMAC
Name	RNA guanine-7 methyltransferase activating subunit
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	HsT19360, C15orf18, MGC2560, RAM
Ensembl gene	ENSG00000169612
Ensembl biotype	protein_coding
OMIM	614547
Entrez	83640

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000304191, ENST00000875578, ENST00000875579, ENST00000875580, ENST00000875581, ENST00000875582, ENST00000933984, ENST00000933985, ENST00000933986, ENST00000933987, ENST00000957626

RefSeq mRNA: 1 — MANE Select: NM_031452 NM_031452

CCDS: CCDS10321

Canonical transcript exons

ENST00000304191 — 4 exons

Exon	Start	End
ENSE00001159540	82989010	82989188
ENSE00001184311	82987336	82987384
ENSE00001184317	82986210	82986369
ENSE00001184323	82989881	82991057

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 94.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.5800 / max 247.2464, expressed in 1806 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148108	22.5800	1806

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	94.66	gold quality
islet of Langerhans	UBERON:0000006	92.82	gold quality
placenta	UBERON:0001987	91.55	gold quality
leukocyte	CL:0000738	90.74	gold quality
monocyte	CL:0000576	90.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.49	gold quality
endometrium	UBERON:0001295	90.40	gold quality
lower esophagus mucosa	UBERON:0035834	89.54	gold quality
esophagus mucosa	UBERON:0002469	89.51	gold quality
gastrocnemius	UBERON:0001388	89.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.35	gold quality
muscle of leg	UBERON:0001383	89.28	gold quality
skeletal muscle organ	UBERON:0014892	89.18	gold quality
rectum	UBERON:0001052	89.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.85	gold quality
pancreas	UBERON:0001264	88.81	gold quality
granulocyte	CL:0000094	88.70	gold quality
smooth muscle tissue	UBERON:0001135	88.68	gold quality
mucosa of transverse colon	UBERON:0004991	88.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.54	gold quality
lymph node	UBERON:0000029	88.20	gold quality
skin of abdomen	UBERON:0001416	87.89	gold quality
zone of skin	UBERON:0000014	87.59	gold quality
body of pancreas	UBERON:0001150	87.51	gold quality
embryo	UBERON:0000922	87.50	gold quality
ganglionic eminence	UBERON:0004023	87.50	gold quality
prefrontal cortex	UBERON:0000451	87.44	gold quality
skin of leg	UBERON:0001511	87.35	gold quality
esophagus	UBERON:0001043	87.20	gold quality
cortical plate	UBERON:0005343	87.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting RAMAC, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8075	99.97	67.20	962
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-7162-3P	99.89	68.16	1682

Literature-anchored findings (GeneRIF, showing 4)

• RAM is an essential component of the core gene expression machinery (PMID:22099306)
• Data suggest that RAM/FAM103A1 has three domains: N-terminal activation domain (RAD); central RNA-binding domain (NR domain); and C-terminal nuclear localization domain (QYP) which contains two nuclear localization signal sequences. (PMID:24200467)
• RNMT-RAM complex coordinates mRNA processing with ribosome production. (PMID:27934633)
• Mechanism of allosteric activation of human RNMT by RAM has been reported. (PMID:31329932)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ramac	ENSMUSG00000038646
mus_musculus	Ramacl	ENSMUSG00000074826
rattus_norvegicus	Ramac	ENSRNOG00000019426

Paralogs (1): RAMACL (ENSG00000235272)

Protein

Protein identifiers

RNA guanine-N7 methyltransferase activating subunit — Q9BTL3 (reviewed: Q9BTL3)

Alternative names: Protein FAM103A1, RNA guanine-7 methyltransferase activating subunit, RNMT-activating mRNA cap methyltransferase subunit, RNMT-activating mini protein

All UniProt accessions (1): Q9BTL3

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5’-cap structure of mRNAs. Promotes the recruitment of the methyl donor, S-adenosyl-L-methionine, to RNMT. Regulates RNMT expression by a post-transcriptional stabilizing mechanism. Binds RNA.

Subunit / interactions. Interacts with RNMT; this interaction enhances mRNA binding and cap methyltransferase activity.

Subcellular location. Nucleus.

Similarity. Belongs to the RAM family.

RefSeq proteins (1): NP_113640* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028271	RAMAC	Family

Pfam: PF15320

UniProt features (18 total): modified residue 4, compositionally biased region 4, region of interest 3, helix 2, initiator methionine 1, chain 1, turn 1, strand 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5E8J	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTL3-F1	62.23	0.26

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 (4): 2, 36, 85, 86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): GOBP_RNA_METHYLATION, CADWELL_ATG16L1_TARGETS_DN, GOBP_RNA_MODIFICATION, GOBP_RNA_CAPPING, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_METHYLATION, MODULE_114, PETRETTO_HEART_MASS_QTL_CIS_UP, CASTELLANO_HRAS_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, GOCC_TRANSFERASE_COMPLEX, GOCC_METHYLTRANSFERASE_COMPLEX, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY

GO Biological Process (3): 7-methylguanosine mRNA capping (GO:0006370), RNA 5’-cap (guanine-N7)-methylation (GO:0106005), mRNA processing (GO:0006397)

GO Molecular Function (4): RNA binding (GO:0003723), enzyme activator activity (GO:0008047), molecular function activator activity (GO:0140677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), mRNA capping enzyme complex (GO:0031533), mRNA cap methyltransferase RNMT:RAMAC complex (GO:0160130)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
7-methylguanosine RNA capping	2
mRNA processing	1
RNA (guanine-N7)-methylation	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
molecular function regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
methyltransferase complex	1

Protein interactions and networks

STRING

222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAMAC	RNMT	O43148	950
RAMAC	RNGTT	O60942	647
RAMAC	CMTR1	Q8N1G2	509
RAMAC	CMTR2	Q8IYT2	480
RAMAC	C15orf40	Q8WUR7	475
RAMAC	FSD2	A1L4K1	380
RAMAC	TMEM209	Q96SK2	359
RAMAC	STRADB	Q9C0K7	349
RAMAC	DHRSX	Q8N5I4	321
RAMAC	TM6SF1	Q9BZW5	312
RAMAC	BTBD1	Q9H0C5	311
RAMAC	HDGFL3	Q9Y3E1	310
RAMAC	PDILT	Q8N807	305
RAMAC	DGCR2	P98153	260
RAMAC	AP3B2	Q13367	258

IntAct

172 interactions, top by confidence:

A	B	Type	Score
RNMT	RAMAC	psi-mi:“MI:0915”(physical association)	0.810
RAMAC	RNMT	psi-mi:“MI:0914”(association)	0.810
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
RAMAC	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
INCA1	RAMAC	psi-mi:“MI:0915”(physical association)	0.720
RAMAC	KRT31	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	RAMAC	psi-mi:“MI:0915”(physical association)	0.720
RAMAC	INCA1	psi-mi:“MI:0915”(physical association)	0.720
KRT31	RAMAC	psi-mi:“MI:0915”(physical association)	0.720
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
EIF4E	RNMT	psi-mi:“MI:0407”(direct interaction)	0.630
BAG4	RAMAC	psi-mi:“MI:0915”(physical association)	0.600
TRIM42	RAMAC	psi-mi:“MI:0915”(physical association)	0.560
DAB1	RAMAC	psi-mi:“MI:0915”(physical association)	0.560
RAMAC	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	RAMAC	psi-mi:“MI:0915”(physical association)	0.560
RAMAC	RBMY1F	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	RAMAC	psi-mi:“MI:0915”(physical association)	0.560
RAMAC	DAB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (94): FAM103A1 (Two-hybrid), FAM103A1 (Two-hybrid), FAM103A1 (Two-hybrid), FAM103A1 (Two-hybrid), FAM103A1 (Two-hybrid), LZTS2 (Two-hybrid), RBMY1F (Two-hybrid), TRIM42 (Two-hybrid), INCA1 (Two-hybrid), FAM103A1 (Two-hybrid), RHOXF2 (Two-hybrid), FAM103A1 (Two-hybrid), FAM103A1 (Two-hybrid), EXOC7 (Co-fractionation), FAM103A1 (Co-fractionation)

ESM2 similar proteins: A0A3B3IU46, A0JMU8, A1L1K8, A2RV70, O94432, P07733, P45978, P46553, P90897, Q09801, Q09911, Q14444, Q1LZB6, Q24669, Q28F29, Q28HC9, Q2HJG4, Q5CZI8, Q5JVS0, Q5M9G3, Q5R9Q6, Q5UR41, Q5ZMS6, Q60865, Q66HC1, Q6CVS3, Q6FJC7, Q6NRP6, Q6NRY1, Q6NYG6, Q6P0F4, Q6P1U3, Q75A59, Q8CGZ0, Q8IWX8, Q8TAP9, Q8VDM6, Q91W18, Q9BTL3, Q9BUJ2

Diamond homologs: A0A3B3IU46, Q28HC9, Q5R9Q6, Q9BTL3, Q9CQY2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RAMAC	“up-regulates activity”	RNMT	binding
ERK1/2	“down-regulates quantity by destabilization”	RAMAC	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Processing of Capped Intron-Containing Pre-mRNA	7	12.8×	3e-04
mRNA Polyadenylation	6	11.7×	2e-03
Neddylation	7	7.4×	4e-03
mRNA Splicing - Major Pathway	6	7.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

435 predictions. Top by Δscore:

Variant	Effect	Δscore
15:82986366:GCGG:G	donor_gain	1.0000
15:82986368:GG:G	donor_gain	1.0000
15:82986369:GG:G	donor_gain	1.0000
15:82987330:CCACA:C	acceptor_loss	1.0000
15:82987331:CACA:C	acceptor_loss	1.0000
15:82987332:ACAG:A	acceptor_loss	1.0000
15:82987333:CAGAT:C	acceptor_loss	1.0000
15:82987334:A:AG	acceptor_gain	1.0000
15:82987335:G:GC	acceptor_loss	1.0000
15:82987335:G:GG	acceptor_gain	1.0000
15:82987382:GGG:G	donor_gain	1.0000
15:82987383:GGG:G	donor_gain	1.0000
15:82987384:GGT:G	donor_loss	1.0000
15:82987385:G:GA	donor_loss	1.0000
15:82987385:G:GG	donor_gain	1.0000
15:82987386:T:G	donor_loss	1.0000
15:82989007:C:G	acceptor_gain	1.0000
15:82989008:A:AG	acceptor_gain	1.0000
15:82989009:G:GA	acceptor_gain	1.0000
15:82989009:GA:G	acceptor_gain	1.0000
15:82989009:GAT:G	acceptor_gain	1.0000
15:82989009:GATT:G	acceptor_gain	1.0000
15:82989142:G:GT	donor_gain	1.0000
15:82989143:A:T	donor_gain	1.0000
15:82989188:GGTG:G	donor_loss	1.0000
15:82989189:G:GG	donor_gain	1.0000
15:82989189:GTGT:G	donor_loss	1.0000
15:82989190:T:A	donor_loss	1.0000
15:82989879:A:AG	acceptor_gain	1.0000
15:82989879:A:AT	acceptor_loss	1.0000

AlphaMissense

780 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:82989061:T:C	F15L	0.978
15:82989063:T:A	F15L	0.978
15:82989063:T:G	F15L	0.978
15:82989073:T:C	F19L	0.977
15:82989075:C:A	F19L	0.977
15:82989075:C:G	F19L	0.977
15:82989095:A:C	Y26S	0.976
15:82989094:T:G	Y26D	0.969
15:82989145:T:A	W43R	0.963
15:82989145:T:C	W43R	0.963
15:82989074:T:C	F19S	0.951
15:82989094:T:A	Y26N	0.942
15:82989094:T:C	Y26H	0.939
15:82989147:G:C	W43C	0.930
15:82989147:G:T	W43C	0.930
15:82989062:T:C	F15S	0.918
15:82989049:T:C	F11L	0.917
15:82989051:T:A	F11L	0.917
15:82989051:T:G	F11L	0.917
15:82989086:A:T	D23V	0.914
15:82989062:T:G	F15C	0.906
15:82989095:A:G	Y26C	0.904
15:82989107:T:C	L30P	0.897
15:82989086:A:C	D23A	0.885
15:82989085:G:C	D23H	0.880
15:82989061:T:A	F15I	0.878
15:82989072:A:C	R18S	0.876
15:82989072:A:T	R18S	0.876
15:82989074:T:G	F19C	0.868
15:82989137:T:A	V40D	0.865

dbSNP variants (sampled 300 via entrez): RS1000016975 (15:82985575 TAAC>T), RS1000967513 (15:82986588 G>A), RS1001042580 (15:82986842 C>T), RS1001317614 (15:82991216 G>T), RS1001369387 (15:82991382 T>C), RS1001834650 (15:82991343 G>A), RS1002259289 (15:82985280 T>C), RS1003044557 (15:82989825 CAT>C), RS1004083104 (15:82986209 C>G,T), RS1005490426 (15:82987176 C>G), RS1005781320 (15:82989516 T>A,C), RS1006570751 (15:82988287 G>A), RS1006903541 (15:82990505 T>C), RS1007156344 (15:82984272 T>C), RS1007265366 (15:82988805 G>T)

Disease associations

OMIM: gene MIM:614547 | 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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Atrazine	decreases expression	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Disulfiram	affects binding, decreases expression	1
Formaldehyde	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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