Gene Panels & Activity Scores

ExposoGraph ships with curated reference gene panels and CPIC-standardized activity scores from the CarcinoGenomic Platform (Tables 3–6).

Each seed gene now includes structured database provenance, and the package exposes a formal source manifest through CURATION_SOURCE_MANIFEST. The manuscript-aligned primary curation sources are IARC, KEGG, PharmVar, CPIC, CTD, GTEx, and PubMed. ExposoGraph also uses NCBI Gene and ClinPGx as supporting implementation sources for stable identifiers and pharmacogene coverage.

The curated KEGG pathway catalog exposed through REFERENCE_KEGG_PATHWAYS currently tracks hsa00980 (xenobiotic metabolism by cytochrome P450), hsa00140 (steroid hormone biosynthesis), hsa05204 (chemical carcinogenesis - DNA adducts), and hsa05208 (chemical carcinogenesis - reactive oxygen species).

Terminology:

• Tier refers to panel priority or inclusion level.

• Phase is reserved for Phase I, II, and III metabolism/transport labels.

• DNA repair genes are classified by repair class such as BER, NER, or Direct Reversal.

Tier 1: Core Panel (13 genes)

The core carcinogen-metabolizing enzyme panel:

Gene	Classification	Role	Detail
CYP1A1	Phase I	Activation	PAH diol-epoxide formation; AhR-inducible; extrahepatic expression
CYP1A2	Phase I	Activation	HCA and aromatic amine activation; AhR-inducible; hepatic
CYP1B1	Phase I	Activation	PAH and estrogen activation; 4-OH-estradiol formation
CYP2A6	Phase I	Activation	NNK and nitrosamine activation; nicotine metabolism
CYP2E1	Phase I	Activation	Small-molecule carcinogen activation; ethanol, benzene, NDMA
CYP3A4	Phase I	Activation	Aflatoxin B1 8,9-epoxidation; broad substrate range
GSTM1	Phase II	Detoxification	GSH conjugation of PAH diol-epoxides; null polymorphism common
GSTT1	Phase II	Detoxification	GSH conjugation of small electrophiles; null polymorphism common
GSTP1	Phase II	Detoxification	GSH conjugation of BPDE and PAH diol-epoxides
NAT2	Phase II	Mixed	N-acetylation of aromatic amines; rapid vs slow acetylator
EPHX1	Phase II	Mixed	Microsomal epoxide hydrolysis; activation and detoxification
UGT1A1	Phase II	Detoxification	Glucuronidation of PAH metabolites and bilirubin
NQO1	Phase II	Detoxification	Two-electron quinone reduction; prevents ROS from redox cycling

Tier 2: Extended Panel (23 genes)

Additional Phase I, II, III, and DNA repair genes:

Gene	Classification	Role	Detail
SULT1A1	Phase II	Detoxification	Sulfation of phenolic compounds, HCA intermediates
NAT1	Phase II	Mixed	O-acetylation of aromatic/heterocyclic amines in peripheral tissues
UGT2B7	Phase II	Detoxification	Glucuronidation of steroid hormones, carcinogen metabolites
UGT2B17	Phase II	Detoxification	Glucuronidation of testosterone, DHT, and related androgen metabolites
SULT1E1	Phase II	Detoxification	High-affinity estrogen sulfotransferase; estradiol and catechol-estrogen inactivation
COMT	Phase II	Detoxification	O-methylation of catechol estrogens; limits redox-cycling estrogen metabolites
ABCB1	Phase III	Transport	P-gp; ATP-driven efflux of hydrophobic xenobiotics
ABCC2	Phase III	Transport	MRP2; export of GSH/glucuronide/sulfate conjugates
ABCG2	Phase III	Transport	BCRP; efflux of PAHs, PhIP, porphyrins
XRCC1	DNA Repair (BER)	Repair	BER scaffold protein; oxidative/alkylation DNA damage
XPC	DNA Repair (NER)	Repair	GG-NER damage sensor; bulky DNA adducts from PAHs
ERCC2/XPD	DNA Repair (NER)	Repair	NER helicase; unwinds DNA at damage sites
OGG1	DNA Repair (BER)	Repair	8-oxoguanine DNA glycosylase; oxidative DNA damage
MGMT	DNA Repair (Direct Reversal)	Repair	Direct reversal of O6-alkylguanine; suicidal repair enzyme
CYP2C9	Phase I	Mixed	Oxidation of PAH metabolites; major drug-metabolizing CYP
CYP2C19	Phase I	Mixed	Minor procarcinogen activation; nitrosamine metabolism
CYP2D6	Phase I	Mixed	Minor NNK activation; dual PGx/carcinogen-risk reporting
CYP2A13	Phase I	Activation	Primary lung NNK-metabolizing CYP; tobacco-smoke activation
CYP17A1	Phase I	Activation	Steroid 17alpha-hydroxylase/17,20-lyase; androgen precursor synthesis
SRD5A1	Phase I	Activation	5alpha-reductase type 1; peripheral testosterone-to-DHT conversion
SRD5A2	Phase I	Activation	5alpha-reductase type 2; major DHT-forming enzyme in prostate tissues
CYP19A1	Phase I	Activation	Aromatase; converts androgen precursors to estrogens
AKR1C3	Phase I	Mixed	Local androgen/estrogen activation with quinone-reductase overlap

Activity Scores

ExposoGraph currently ships activity-score tables for 18 genes. These tables mix two evidence classes:

• guideline-backed pharmacogene resources, primarily surfaced through ClinPGx/PharmVar

• research-use literature-derived mappings for carcinogen metabolism and DNA repair genes

They should therefore be treated as referenced curation aids, not as a full clinical pharmacogenomics engine. Each gene now has supporting evidence metadata available through ACTIVITY_SCORE_METADATA.

Each per-allele entry has:

• allele — Star allele or variant name

• value — Numeric activity score (0.0 = no function, 1.0 = normal, 2.0 = ultrarapid)

• phenotype — Functional interpretation

• confidence — High or Moderate

Example: CYP2D6

Allele	Score	Phenotype	Confidence
*1, *2, *35	1.0	Normal Metabolizer	High
*9, *17, *29, *41	0.5	NM (lower range)	High
*10	0.25	NM (lowest); IM	High
*3, *4, *5, *6, *40	0.0	Poor Metabolizer	High
*1x2, *2x2 (dupl.)	2.0	Ultrarapid Metabolizer	High

The full set covers 18 genes. See ACTIVITY_SCORES for the score table and ACTIVITY_SCORE_METADATA for the references.

Usage

from ExposoGraph import (
    build_full_panel,
    get_activity_scores,
    get_activity_score_references,
)

# Load all 36 genes into a KnowledgeGraph
kg = build_full_panel()

# Look up scores for a specific gene
scores = get_activity_scores("CYP1A1")
for entry in scores:
    print(f"{entry['allele']}: {entry['value']} — {entry['phenotype']}")

# Inspect the supporting references
for ref in get_activity_score_references("CYP1A1") or []:
    print(ref["source_db"], ref.get("pmid") or ref.get("record_id"), ref["url"])